| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 1999;100:292-298.)
© 1999 American Heart Association, Inc.
Basic Science Reports |
Endothelial Dysfunction in Chronic Myocardial Infarction Despite Increased Vascular Endothelial Nitric Oxide Synthase and Soluble Guanylate Cyclase Expression
Role of Enhanced Vascular Superoxide Production
From the II. Medizinische Klinik, Universitätsklinikum Mannheim, Fakultät für Klinische Medizin Mannheim der Universität Heidelberg, and Institut für Kardiovaskuläre Physiologie, Klinikum der J.W. Goethe-Universität, Frankfurt am Main (A.B., R.B.), Germany.
Correspondence to Dr Johann Bauersachs, II. Medizinische Klinik, Klinikum, Theodor-Kutzer-Ufer, D-68135 Mannheim, Germany. E-mail johann.bauersachs{at}med2.ma.uni-heidelberg.de
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
Background—Endothelial dysfunction of the peripheral vasculature is a well-known phenomenon in congestive heart failure that contributes to the elevated peripheral resistance; however, the underlying mechanisms have not yet been clarified.
Methods and Results—Dilator responses, the expression of protein and mRNA of the endothelial nitric oxide synthase (eNOS), inducible NOS (iNOS), and soluble guanylate cyclase (sGC), and superoxide anion (O2-) and peroxynitrite production were determined in aortic rings from Wistar rats 8 weeks after myocardial infarction and compared with those in sham-operated animals. In rats with heart failure, the concentration-response curve of the endothelium-dependent vasodilator acetylcholine (after preconstriction with phenylephrine) was significantly shifted to the right, and the maximum relaxation was attenuated. Determination of expression levels of the 2 key enzymes for NO-mediated dilations, eNOS and sGC, revealed a marked upregulation of both enzymes in aortas from rats with heart failure, whereas iNOS expression was not changed. Pretreatment with exogenous superoxide dismutase partially restored the acetylcholine-induced relaxation in aortas from rats with heart failure. Aortic basal and NADH-stimulated O2- production assessed by use of lucigenin-enhanced chemiluminescence was significantly elevated in rats with chronic myocardial infarction. Peroxynitrite-mediated nitration of protein tyrosine residues was not different between the 2 groups of rats.
Conclusions—These results demonstrate that endothelial dysfunction in ischemic heart failure occurs despite an enhanced vascular eNOS and sGC expression and can be attributed to an increase in vascular O2- production by an NADH-dependent oxidase. By inactivation of NO, O2- production appears to be an essential mechanism for the endothelial dysfunction observed in heart failure.
Key Words: endothelium • endothelium-derived factors • myocardial infarction • heart failure • free radicals
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Endothelial dysfunction of the peripheral vasculature contributes to the elevated peripheral vascular resistance in patients with heart failure,1 2 3 as well as several animal models of cardiac dysfunction.4 5 6 However, the underlying mechanisms may be complex and have not yet been clarified. One attractive hypothesis appears to be a decrease in the production of endothelium-derived nitric oxide (NO). In a heart failure model of ventricular pacing in dogs, an endothelial hyporesponsiveness in the coronary circulation and an attenuated expression of the endothelial NO synthase (eNOS) in the aorta have been described.7 8 In contrast, other studies reported enhanced basal production of NO in heart failure,6 9 which might originate from the inducible NOS (iNOS) in the vasculature, because the expression of this high-output NO-generating enzyme has been shown in hearts from patients with dilated cardiomyopathy.10
In other pathophysiological states, such as hypercholesterolemia and hypertension, compelling evidence suggests that endothelial dysfunction results from increased vascular production of superoxide anion (O2-).11 12 13 Because O2- rapidly scavenges NO within the vascular wall, a reduction of bioactive NO might occur despite an increased NO generation.14 15 In patients suffering from heart failure, elevated levels of plasma lipid peroxides as a marker of oxidative stress have been observed.16 This is further supported by the fact that the impaired flow-induced NO-mediated dilation in patients with heart failure can be restored by short-term treatment with high doses of the antioxidant vitamin C.17
In addition, more recently, alterations of the effector system of NO, in particular a reduced expression of the cGMP-forming soluble guanylate cyclase (sGC), were identified as an important mechanism of dilator dysfunction in hypertension.18
With regard to heart failure, no data are available on O2- production within the vascular wall or on the potential alterations of the expression of smooth muscle sGC. Moreover, the influence of heart failure on vascular NOS expression is still controversial. Chronic myocardial infarction in the rat is considered to be a useful model to study the pathophysiological sequelae of heart failure. Indeed, the beneficial effects of ACE inhibitors were predicted from results obtained in this experimental model.19 In rats with heart failure due to myocardial infarction, endothelium-dependent relaxations, still normal at 1 week after coronary ligature, are reduced at 4 weeks and progressively worsen with time.20
The aim of the present study was therefore to identify the potential mechanisms underlying endothelial dysfunction in heart failure by the simultaneous determination of endothelium-dependent dilator responses, the expression of the key enzymes of the NO/cGMP system, and O2- formation in the aorta of rats 8 weeks after myocardial infarction.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Myocardial Infarction: Hemodynamic Measurements
Left coronary artery ligations were performed in adult female Wistar rats (250 to 300 g) as previously described.21 Briefly, under ether anesthesia, the thorax was opened, the heart exteriorized, and a ligature placed around the proximal left coronary artery. Sham-operated rats were treated similarly except that the operative procedure did not produce a detectable infarction. Hemodynamic studies were performed 8 weeks after coronary artery ligation as described.21 Briefly, rats were anesthetized with ether, tracheotomized, and ventilated. Saline-filled catheters were advanced from the right carotid artery and jugular vein into the left ventricle and right atrium and connected to a Millar micrometer and Statham transducer. Left ventricular systolic and diastolic pressures, mean arterial pressure, and heart rate were measured under light ether anesthesia and spontaneous respiration.
Infarct size was determined histologically by planimetry as described21 after formalin fixation, and only rats with large infarcts (>40%) were included in the study of vascular reactivity.
Measurement of Plasma Renin Activity
Plasma renin activity was measured as described
previously21 with a commercial test kit (Sorin Biomedica
Diagnostic).
Vascular Reactivity Studies
The descending thoracic aorta was dissected after removal of the
heart, cleaned of connective tissue, and cut into 3 sections as
described.18 The upper section (15 mm) was
immediately frozen in liquid nitrogen for Western blot
analysis. The lower section (10 mm) was used for
measurement of O2-
production, and the remainder was cut into rings 3 mm long
that were mounted in an organ bath (Föhr Medical Instruments) for
isometric force measurement. The rings were equilibrated for 30 minutes
under a resting tension of 2 g in oxygenated (95%
O2/5% CO2) Krebs-Henseleit
solution (pH 7.4, 37°C) of the following composition (mmol/L): NaCl
118, KCl 4.7, MgSO4 1.2,
CaCl2 1.6,
K2HPO4 1.2,
NaHCO3 25, and glucose 12, and the
cyclooxygenase inhibitor diclofenac
1 µmol/L. Rings were repeatedly contracted by KCl 50 mmol/L
until reproducible responses were obtained. Thereafter, the rings were
preconstricted with phenylephrine 0.3 to 1 µmol/L to
comparable constriction levels, and the relaxant response to cumulative
doses of acetylcholine and to sodium nitroprusside was assessed with or
without prior inhibition of the endogenous superoxide
dismutase (SOD) by use of diethyldithiocarbamate (DETC, 1 mmol/L,
40 minutes, followed by repeated washout). In additional experiments,
the effect of exogenous SOD on relaxant responses was assessed.
Analysis of eNOS and sGC Expression by Reverse
Transcription–Polymerase Chain Reaction
Total RNAs were extracted according to the method of Chomczynski
and Sacchi.22 For the reverse transcription (RT), 2 µg
total RNA was incubated with 200 U reverse transcriptase (Gibco), dNTP
125 µmol/L, oligo(dT) 200 ng, and reaction buffer in a final
volume of 20 µL at 37°C for 60 minutes. After a final denaturation
at 94°C for 7 minutes, 5 µL of cDNA was subjected to polymerase
chain reaction (PCR) consisting of denaturation at 94°C for 1 minute,
followed by 90 seconds of annealing at 52°C for eNOS/GAPDH or 81°C
for 
1- and 65°C for
ß1-subunits from the sGC and 90 seconds of
elongation at 72°C for 25 to 30 cycles. The last cycle ended with 7
minutes of elongation at 72°C. The primers used (Table 1
) were chosen as previously
described.15 18 23 The PCR contained 0.4 µmol/L of
each primer, dNTP 200 µmol/L, MgCl2 1
mmol/L reaction buffer, and 2.5 U Taq polymerase (Promega)
in a final volume of 50 µL. The amplified cDNAs were
size-fractionated by agarose gel electrophoresis, visualized under UV
light by use of ethidium bromide staining, transferred to nylon
membrane (Hybond-N, Amersham), and hybridized with a
32P-labeled eNOS fragment obtained from the
cloned bovine eNOS cDNA, 32P-labeled GAPDH
fragment isolated from PCR, and 32P-labeled human
1- and ß1-subunit
cDNAs. The cDNAs were quantified after autoradiography
by scanning densitometry normalized by comparison with GAPDH cDNA.
|
Western Blot Analysis
After alcohol precipitation of the phenol phase obtained after
the guanidinium isothiocyanate/phenol/chloroform extraction
method,22 crude protein extracts (100 µg) were subjected
to SDS-PAGE electrophoresis and transferred to nitrocellulose membranes
as described.24 Proteins were detected by their respective
antibodies and visualized by enhanced chemiluminescence; the
autoradiographs were analyzed by scanning densitometry.
Determination of cGMP in Aortic Rings
For the determination of cGMP accumulation25 in rat
aortic segments without confounding effects of
endothelium-derived NO, cGMP levels were determined
after denudation of the endothelium under basal
conditions and after stimulation with sodium nitroprusside 1
µmol/L for 2 minutes in the presence of the phosphodiesterase
inhibitor isobutylmethylxanthine
(IBMX, 0.3 mmol/L) and freeze-clamped.
Measurement of Superoxide Anion and Peroxynitrite
Formation
The O2- generation of
the rings was assessed by lucigenin-enhanced chemiluminescence as
described previously.18 Briefly, aortic segments (5
mm) were transferred into tubes containing 0.5 mL HEPES buffer and
maintained at 37°C for at least 30 minutes before lucigenin 250
µmol/L was added. The luminometer (LKB-Wallac 1251) was set to report
arbitrary units of light emitted and integrated over a 30-second
interval, and repeated measurements were made over 3 minutes and
averaged. The specific chemiluminescence signal was calculated after
subtraction of background activity and expressed as counts per
minute per milligram dry weight of samples (cpm/mg). Peroxynitrite
formation was assessed in a similar protocol using luminol 250
µmol/L.
Materials
All biochemicals were obtained in the highest purity available
from Sigma Chemical Co. The [-32P]dCTP was
purchased from Hartmann Analytic. The cloned bovine eNOS cDNA was a
gift from D.G. Harrison, Emory University, Atlanta, Ga. The monoclonal
eNOS antibody was purchased from Transduction Laboratories (Affiniti),
and the antibody against the sGC ß1-subunit was
kindly provided by Dr Peter Yuen, Memphis, Tenn.
Statistics
Dilator responses were given as percentage dilatation relative
to the preconstriction level. All data in the figures and in the text
are expressed as mean±SEM of experiments with aortic segments from n
different animals. Statistical analysis was performed by 1-way
ANOVA followed by a Bonferroni t test or by the 2-tailed
Student's t test for unpaired data, where appropriate, with
probability values of <0.05 considered statistically
significant.
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Global Parameters
Global parameters of heart failure rats and sham-operated animals are shown in Table 2
. Infarct size was 45±1%. Mean
arterial blood pressure, left ventricular
systolic pressure, and dP/dtmax were
significantly lower in rats with chronic myocardial infarction, whereas
left ventricular end-diastolic pressure was
elevated. Plasma renin activity was significantly higher in rats with
heart failure. Therefore, these rats demonstrated heart failure in a
compensated stage.
|
Vasodilator Responses in Aortic Rings
In phenylephrine-preconstricted aortic rings,
acetylcholine elicited a concentration-dependent relaxation that was
blunted in aortas from rats with cardiac dysfunction (Figure 1A). Acetylcholine-induced relaxations
were mediated by NO because they were abolished after incubation with
the NOS inhibitor
NG-nitro-L-arginine
0.3 mmol/L for 30 minutes (data not shown).
Endothelium-independent relaxations induced by sodium
nitroprusside were slightly but not significantly attenuated at lower
concentrations in rats with heart failure, and maximum relaxation was
not different (100%) in the 2 groups of rats (Figure 1B).
|
) vs
sham-operated (•) animals. Results are expressed as mean±SEM from 8
to 10 separate experiments. *P<0.05,
**P<0.01 vs sham.
NO- and cGMP-Generating Enzymes in the Aorta
To elucidate whether the attenuation of
endothelium-dependent relaxation is the result of an
alteration in the expression of the key enzymes of NO-mediated
dilation, the expression of protein and mRNA of both eNOS and iNOS as
well as sGC was determined in aortic segments from rats with heart
failure and sham-operated animals by Western blot and RT-PCR. As shown
in Figure 2, eNOS mRNA and protein levels
were found to be significantly increased in aortas from rats with heart
failure compared with sham-operated animals (2.9- and 2.1-fold
increase, respectively, P<0.05, n=4), whereas the iNOS
expression in the thoracic aorta, hardly detectable by Western blot
analysis (Figure 3A), remained
unchanged.
|
|
In addition, Western blot analysis performed on whole aortic
protein extracts showed that the protein level of the
ß1-subunit of the sGC was markedly enhanced in
rats with myocardial infarction (Figure 3B
, 2.5-fold increase,
P<0.05, n=4), whereas the RT-PCR analysis failed to
detect significant differences between infarcted and sham-operated
animals (data not shown).
Effects of Radical Scavengers on Vascular Reactivity and cGMP
Production
Because NO- and cGMP-generating enzymes were found to be
upregulated in rats with heart failure, we investigated the potential
involvement of reactive oxygen species in the alteration of the
endothelial function. The effects of radical scavengers
were studied on the vascular reactivity and cGMP
production.
In phenylephrine-constricted rings, addition of exogenous
SOD 600 U/mL elicited a relaxation that was significantly enhanced in
aortic rings from rats with heart failure (83±3% versus 56±4%,
P<0.01). Furthermore, in the presence of exogenous SOD 200
U/mL, the relaxation induced by submaximal concentrations of
acetylcholine in aortas from rats with chronic cardiac dysfunction was
significantly enhanced (Figure 4).
|
Conversely, after inhibition of the endogenous SOD by use
of DETC 1 mmol/L for 40 minutes, the acetylcholine-induced
relaxation in aortic rings was markedly depressed in aortas from
sham-operated rats and abolished in animals with chronic myocardial
infarction (Figure 4).
Basal levels of cGMP in aortas from rats with heart failure (2.4±0.4
pmol/mg protein) were not different from those in sham-operated animals
(1.5±0.3 pmol/mg protein, n=6, Figure 5). Stimulation with sodium nitroprusside
induced a marked increase in cGMP formation, and cGMP levels were lower
in rats with cardiac dysfunction than in sham-operated animals.
However, in the presence of the radical scavenger Tiron 10 mmol/L,
sodium nitroprusside–induced cGMP formation was significantly enhanced
in aortas from rats with heart failure (Figure 5).
|
Production of Superoxide Anions and Peroxynitrite in
Aortic Segments
Finally, we assessed the production of
O2- and of peroxynitrite
generated by aortic rings by lucigenin- and luminol-enhanced
chemiluminescence, respectively.
O2- release was greater in
aortas from rats with chronic myocardial infarction (Figure 6A). Removal of the
endothelium slightly but not significantly reduced
radical production in both groups (Figure 6A). After
addition of NADH 100 µmol/L,
O2- formation was markedly
stimulated and significantly higher in aortas from rats with heart
failure (Figure 6B).
|
The luminol-mediated luminescence as indicator of peroxynitrite formation was hardly detectable and not different in aortas from rats with chronic myocardial infarction and those from sham-operated animals. Moreover, Western blot analysis of aortic proteins with a specific antibody against nitrotyrosine to detect peroxynitrite-mediated nitration of tyrosine residues showed no increase in nitrotyrosine in rats with heart failure compared with sham-operated animals (data not shown).
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
In the present study, we observed a pronounced endothelial dysfunction in rats with chronic myocardial infarction despite a marked upregulation in the expression of 2 key enzymes of vasorelaxation: eNOS, regulating the synthesis of the most important vasodilator, NO, and its target enzyme in smooth muscle cells, sGC. Our data suggest that even this upregulation is not sufficient to compensate for the increased formation of O2-, which rapidly inactivates NO.
Expression of eNOS, iNOS, and sGC
Heart failure is associated with an endothelial
dysfunction of coronary arteries as well as large conductance
and peripheral arteries, with considerable implications for
myocardial perfusion, cardiac workload, and peripheral
vascular resistance.1 7 26 From these functional studies,
the mechanism underlying the reduction of agonist-stimulated dilator
responses in heart failure has been proposed to be a defective
production of endothelium-derived NO, and in a
heart failure model of ventricular pacing in dogs as well
as in monocrotaline-induced cardiac failure, a reduction of
endothelial NO release was associated with an
attenuated expression of eNOS.8 27 Data on basal
production of NO in heart failure have been controversial:
using the amount of constriction in response to an NOS
inhibitor as an indirect measure for basal NO release, some
investigators found an increase6 9 and speculated that
expression of iNOS in the vasculature may be induced, as has been shown
in hearts from patients with dilated
cardiomyopathy.10 However, other
reports found no difference or even a decrease of basal NO formation in
patients with heart failure.28 29
Our results for the first time provide insights into the mechanisms of the alteration of endothelial function in heart failure after myocardial infarction, which represents the most important cause for cardiac failure in patients. Although in agreement with the results obtained in monocrotaline-induced heart failure,27 iNOS expression was hardly detectable in rats with chronic myocardial infarction, we observed an unexpected marked increase in the expression of eNOS. The association of an increased eNOS expression with a marked attenuation of endothelium-dependent relaxation adds to the mounting evidence that enhanced NO formation or NOS expression does not necessarily imply improved dilator function but rather may even be detrimental15 or at least a failed counterregulatory mechanism. In parallel with our results obtained in the aorta, in the myocardium of spontaneously hypertensive genetically heart failure–prone rats, an upregulation of cardiac eNOS expression has been observed; however, the functional consequences of this were not investigated.30
The second key enzyme for endothelium-dependent dilation, the sGC in smooth muscle cells, is activated after binding of endothelium-derived NO to generate large amounts of cGMP. Recently, an attenuation of aortic sGC expression was recognized as a potential mechanism of reduced dilator response in aged spontaneously hypertensive rats.18 In rats with chronic myocardial infarction, however, we observed an upregulation of sGC expression that was associated with a blunted cGMP formation in response to sodium nitroprusside. Because sGC activity is susceptible to superoxide25 and cGMP production was restored by prior treatment with the radical scavenger Tiron, enhanced production of superoxide anions may be responsible for the reduced activity of sGC despite the increase in its expression. Enhanced degradation of cGMP due to increased phosphodiesterase activity31 is not likely, because our experiments were performed in the continuous presence of a high concentration of a phosphodiesterase inhibitor. An enhanced O2- formation in rats with heart failure appears to account for the paradoxical attenuation of cGMP accumulation despite increased sGC expression.
Oxidative Stress in Heart Failure and Vascular
O2- Formation
Elevated levels of plasma lipid peroxides in patients suffering
from heart failure provide clear evidence of an enhanced oxidative
stress under this condition.16 32 In addition, the
transition from hypertrophy to heart failure in
coarctation-induced hypertension was associated with an increased
oxidative stress and could be prevented by treatment with the
antioxidant vitamin E, thus indicating a
pathophysiological role for oxidative stress in the
pathogenesis of heart failure.33 High doses of vitamin C
were able to restore the impaired NO-mediated dilation in patients with
heart failure,17 and in line with these observations, our
results provide the first direct experimental evidence for an enhanced
release of reactive oxygen species from the vasculature in chronic
ischemic cardiac dysfunction. The source of superoxide
formation appears to be vascular smooth muscle cells, because removal
of the endothelium did not significantly attenuate
radical production. Cultured and native vascular smooth muscle
cells are able to generate superoxide in response to the
vasoconstrictor peptide angiotensin II, which stimulates
the expression of an NAD(P)H-dependent oxidase.13 34
Plasma renin activity as well as tissue ACE activity is markedly
elevated in heart failure.35 Therefore, an enhanced
formation of angiotensin II may lead to an enhanced
vascular superoxide formation through the expression of an
NAD(P)H-dependent oxidase in aortic smooth muscle
cells.13 34 Indeed, the observed upregulation of
NADH-dependent O2- formation in
aortas from rats with chronic myocardial infarction suggests that this
mechanism may be operative in ischemic heart failure.
The deleterious role of O2- formation for endothelial function in ischemic cardiac dysfunction is further strengthened by the observation that exogenous SOD exerted a significantly greater relaxation in rats with chronic myocardial infarction and by the partial restoration of the acetylcholine-induced relaxation in the presence of SOD.
An imbalance between NO and superoxide production with enhanced inactivation of NO, leading to a reduction of bioactive NO despite a normal or even increased generation of NO, has been associated with endothelial dysfunction and appears to be a common feature of many cardiovascular diseases, such as hypercholesterolemia and hypertension.11 12 13 15 18 In addition, depending on the pathophysiological circumstances, NO and superoxide may react to the powerful oxidant peroxynitrite, which can form hydroxyl radicals and nitrate protein tyrosine residues.15 However, we detected neither enhanced luminol chemiluminescence nor tyrosine nitration in rats with heart failure, so there was no hint for the formation of peroxynitrite.
In conclusion, our data indicate that an increased NADH-dependent vascular O2- generation represents an important mechanism for the endothelial dysfunction in heart failure by enhancing the inactivation of NO. Even a presumably counterregulatory upregulation of eNOS and sGC is not sufficient to restore endothelium-dependent relaxations.
|
Acknowledgments |
|---|
This work was supported in part by the Deutsche Forschungsgemeinschaft (Ba 1742/1-1) and the Forschungsfonds der Fakultät für Klinische Medizin Mannheim (0067/1997). The authors wish to thank Isabel Winter, Claudia Liebetrau, and Elke Burmeister for expert technical assistance.
Received December 16, 1998; revision received March 15, 1999; accepted March 31, 1999.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
1. Kubo SH, Rector TS, Bank AJ, Williams RE, Heifetz SM. Endothelium-dependent vasodilation is attenuated in patients with heart failure. Circulation. 1991;84:1589–1596.
2. Katz SD, Biasucci L, Sabba C, Strom JA, Jondeau G, Galvao N, Solomon S, Nikolic SD, Forman R, LeJemtel T. Impaired endothelium-mediated vasodilation in the peripheral vasculature of patients with congestive heart failure. J Am Coll Cardiol. 1992;19:918–925.[Abstract]
3. Drexler H, Hayoz D, Münzel T, Hornig B, Just H, Brunner HR, Zelis R. Endothelial function in chronic congestive heart failure. Am J Cardiol. 1992;69:1596–1601.[Medline] [Order article via Infotrieve]
4.
Ontkean M, Gray R, Greenberg B. Diminished
endothelium-derived relaxing factor activity in an
experimental model of chronic heart failure. Circ Res. 1991;69:1088–1096.
5.
Kaiser L, Spickard RC, Olivier NB. Heart failure
depresses endothelium-dependent responses in canine
femoral artery. Am J Physiol. 1989;256:H962–H967.
6.
Drexler H, Lu W. Endothelial
dysfunction of hindquarter resistance vessels in experimental heart
failure. Am J Physiol. 1992;262:H1640–H1645.
7.
Wang J, Sevanian A, Xu XB, Wolin MS, Hintze TH.
Defective endothelium-mediated control of
coronary circulation in conscious dogs after heart failure.
Am J Physiol. 1994;266:H670–H680.
8.
Smith CJ, Sun D, Hoegler C, Roth BS, Zhang X, Zhao G,
Xu XB, Kobari Y, Pritchard K, Sessa WC, Hintze TH. Reduced gene
expression of vascular endothelial NO synthase and
cyclooxygenase-1 in heart failure. Circ
Res. 1996;78:58–64.
9. Habib F, Dutka D, Crossman D, Oakley CM, Cleland JGF. Enhanced basal nitric oxide production in heart failure: another failed counter-regulatory vasodilator mechanism? Lancet. 1994;344:371–373.[Medline] [Order article via Infotrieve]
10.
Haywood GA, Tsao PS, von der Leyen HE, Mann MJ, Keeling
PJ, Trindade PT, Lewis NP, Byrne CD, Rickenbacher PR, Bishopric NH,
Cooke JP, McKenna WJ, Fowler MB. Expression of inducible nitric oxide
synthase in human heart failure. Circulation. 1996;93:1087–1094.
11. Ohara Y, Peterson TE, Harrison DG. Hypercholesterolemia increases endothelial superoxide production. J Clin Invest. 1993;91:2546–2551.
12. Grunfeld S, Hamilton CA, Mesaros S, McClain SW, Dominiczak AF, Bohr DF, Malinski T. Role of superoxide in the depressed nitric oxide production by the endothelium of genetically hypertensive rats. Hypertension. 1995;26(pt 1):854–857.
13. Rajagopalan S, Kurz S, Münzel T, Tarpey M, Freeman BA, Griendling KK, Harrison DG. Angiotensin II-mediated hypertension in the rat increases vascular superoxide production via membrane NADH/NADPH oxidase activation. J Clin Invest. 1996;97:1916–1923.[Medline] [Order article via Infotrieve]
14.
Nava E, Noll G, Lüscher TF. Increased activity of
constitutive nitric oxide synthase in cardiac
endothelium in spontaneous hypertension.
Circulation. 1995;91:2310–2313.
15.
Bouloumié A, Bauersachs J, Linz W,
Schölkens BA, Wiemer G, Fleming I, Busse R.
Endothelial dysfunction coincides with an enhanced NO
synthase expression and superoxide anion production.
Hypertension. 1997;30:934–941.
16.
Belch JJF, Bridges AB, Scott N, Chopra M. Oxygen free
radicals and congestive heart failure. Br Heart J. 1991;65:245–248.
17.
Hornig B, Arakawa N, Kohler C, Drexler H. Vitamin C
improves endothelial function of conduit arteries in
patients with chronic heart failure. Circulation. 1998;97:363–368.
18.
Bauersachs J, Bouloumié A, Mülsch A, Wiemer
G, Fleming I, Busse R. Vasodilator dysfunction in aged spontaneously
hypertensive rats: changes in NO synthase III and soluble guanylyl
cyclase expression, and in superoxide anion production.
Cardiovasc Res. 1998;37:772–779.
19.
Pfeffer JM, Pfeffer MA, Braunwald E. Influence of
chronic captopril therapy on the infarcted left ventricle of the rat.
Circ Res. 1985;57:84–95.
20. Teerlink JR, Clozel M, Fischli W, Clozel JP. Temporal evolution of endothelial dysfunction in a rat model of chronic heart failure. J Am Coll Cardiol. 1993;22:615–620.[Abstract]
21.
Fraccarollo D, Hu K, Galuppo P, Gaudron P, Ertl G.
Chronic endothelin receptor blockade attenuates progressive
ventricular dilatation and improves cardiac function in
rats with myocardial infarction: possible involvement of myocardial
endothelin system in ventricular remodeling.
Circulation. 1997;96:3963–3973.
22. Chomczynski P, Sacchi N. Single step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987;162:156–159.[Medline] [Order article via Infotrieve]
23.
Papapetropoulos A, Marczin N, Mora G, Milici A, Murad
F, Catravas JD. Regulation of vascular smooth muscle soluble guanylyl
cyclase activity, mRNA and protein levels by cAMP-elevating agents.
Hypertension. 1995;26:696–704.
24.
Fleming I, Fisslthaler B, Busse R. Calcium signaling in
endothelial cells involves activation of tyrosine
kinases and leads to the activation of mitogen-activated
protein kinases. Circ Res. 1995;76:522–529.
25. Mülsch A, Bauersachs J, Schäfer A, Stasch JP, Kast R, Busse R. Effect of YC-1, an NO-independent, superoxide-sensitive stimulator of soluble guanylyl cyclase, on smooth muscle responsiveness to nitrovasodilators. Br J Pharmacol. 1997;120:681–689.[Medline] [Order article via Infotrieve]
26.
Ramsey MW, Goodfellow J, Jones CJH, Luddington LA,
Lewis MJ, Henderson AH. Endothelial control of
arterial distensibility is impaired in chronic heart
failure. Circulation. 1994;92:3212–3219.
27. Comini L, Bachetti T, Gaia G, Pasini E, Agnoletti L, Pepi P, Ceconi C, Curello S, Ferrari R. Aorta and skeletal muscle NO synthase expression in experimental heart failure. J Mol Cell Cardiol. 1996;28:2241–2248.[Medline] [Order article via Infotrieve]
28. Mohri M, Egashira K, Tagawa T, Kuga T, Tagawa H, Harasawa Y, Shimokawa H, Takeshita A. Basal release of nitric oxide is decreased in the coronary circulation in patients with heart failure. Hypertension. 1997;30(pt 1):50–56.
29. Kubo SH, Rector TS, Bank AJ, Raij L, Kraemer MD, Tadros P, Beardslee M, Garr MD. Lack of contribution of nitric oxide to basal vasomotor tone in heart failure. Am J Cardiol. 1994;74:1133–1136.[Medline] [Order article via Infotrieve]
30.
Khadour FH, Kao RH, Park S, Armstrong PW, Holycross BJ,
Schulz R. Age-dependent augmentation of cardiac
endothelial NOS in a genetic rat model of heart
failure. Am J Physiol. 1997;273:H1223–H1230.
31. Supaporn T, Sandberg SM, Borgeson DD, Heublein DM, Luchner A, Wei C-M, Dousa T, Burnett JCJ. Blunted cGMP response to agonists and enhanced glomerular cyclic 3',5'-nucleotide phosphodiesterase activities in experimental congestive heart failure. Kidney Int. 1996;50:1718–1725.[Medline] [Order article via Infotrieve]
32.
Keith M, Geranmayegan A, Sole MJ, Kurian R, Robinson A,
Omran A, Jeejeebhoy KN. Increased oxidative stress in patients with
congestive heart failure. J Am Coll Cardiol. 1998;31:1352–1356.
33. Dhalla AK, Hill MF, Singal PK. Role of oxidative stress in transition of hypertrophy to heart failure. J Am Coll Cardiol. 1996;28:506–514.[Abstract]
34.
Griendling KK, Minieri CA, Ollerenshaw JD, Alexander
RW. Angiotensin II stimulates NADH and NADPH oxidase
activity in cultured vascular smooth muscle cells. Circ Res. 1994;74:1141–1148.
35.
Wollert KC, Studer R, von Bülow B, Drexler H.
Survival after myocardial infarction in the rat: role of tissue
angiotensin converting enzyme inhibition.
Circulation. 1994;90:2457–2467.
This article has been cited by other articles:
 |
|
 |
|
  I. H. Zucker, H. D. Schultz, K. P. Patel, W. Wang, and L. Gao Regulation of central angiotensin type 1 receptors and sympathetic outflow in heart failure Am J Physiol Heart Circ Physiol, November 1, 2009; 297(5): H1557 - H1566. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Koba, Z. Gao, and L. I. Sinoway Oxidative stress and the muscle reflex in heart failure J. Physiol., November 1, 2009; 587(21): 5227 - 5237. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Apostolakis, G. Y.H. Lip, and E. Shantsila Monocytes in heart failure: relationship to a deteriorating immune overreaction or a desperate attempt for tissue repair? Cardiovasc Res, October 28, 2009; (2009) cvp327v2. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Bagi Mechanisms of coronary microvascular adaptation to obesity Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2009; 297(3): R556 - R567. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Tsutsui, S. Kinugawa, and S. Matsushima Mitochondrial oxidative stress and dysfunction in myocardial remodelling Cardiovasc Res, February 15, 2009; 81(3): 449 - 456. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-M. Lu, F. Han, N. Shioda, S. Moriguchi, Y. Shirasaki, Z.-H. Qin, and K. Fukunaga Phenylephrine-Induced Cardiomyocyte Injury Is Triggered by Superoxide Generation through Uncoupled Endothelial Nitric-Oxide Synthase and Ameliorated by 3-[2-[4-(3-Chloro-2-methylphenyl)-1-piperazinyl]ethyl]-5,6-dimethoxyindazole (DY-9836), a Novel Calmodulin Antagonist Mol. Pharmacol., January 1, 2009; 75(1): 101 - 112. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Donato, I. Eskurza, K. L. Jablonski, L. B. Gano, G. L. Pierce, and D. R. Seals Cytochrome P-450 2C9 signaling does not contribute to age-associated vascular endothelial dysfunction in humans J Appl Physiol, October 1, 2008; 105(4): 1359 - 1363. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Fraccarollo, J. D. Widder, P. Galuppo, T. Thum, D. Tsikas, M. Hoffmann, H. Ruetten, G. Ertl, and J. Bauersachs Improvement in Left Ventricular Remodeling by the Endothelial Nitric Oxide Synthase Enhancer AVE9488 After Experimental Myocardial Infarction Circulation, August 19, 2008; 118(8): 818 - 827. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. L. Marro, C. Peiro, C. M. Panayiotou, R. S. Baliga, S. Meurer, H. H. H. W. Schmidt, and A. J. Hobbs Characterization of the Human {alpha}1{beta}1 Soluble Guanylyl Cyclase Promoter: KEY ROLE FOR NF-{kappa}B(p50) AND CCAAT-BINDING FACTORS IN REGULATING EXPRESSION OF THE NITRIC OXIDE RECEPTOR J. Biol. Chem., July 18, 2008; 283(29): 20027 - 20036. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. P. C. Davel, L. E. Fukuda, L. L. De Sa, C. D. Munhoz, C. Scavone, D. Sanz-Rosa, V. Cachofeiro, V. Lahera, and L. V. Rossoni Effects of isoproterenol treatment for 7 days on inflammatory mediators in the rat aorta Am J Physiol Heart Circ Physiol, July 1, 2008; 295(1): H211 - H219. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. K. Soukhova-O'Hare, R. V. Ortines, Y. Gu, A. D. Nozdrachev, S. D. Prabhu, and D. Gozal Postnatal Intermittent Hypoxia and Developmental Programming of Hypertension in Spontaneously Hypertensive Rats: The Role of Reactive Oxygen Species and L-Ca2+ Channels Hypertension, July 1, 2008; 52(1): 156 - 162. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Jebelovszki, C. Kiraly, N. Erdei, A. Feher, E. T. Pasztor, I. Rutkai, T. Forster, I. Edes, A. Koller, and Z. Bagi High-fat diet-induced obesity leads to increased NO sensitivity of rat coronary arterioles: role of soluble guanylate cyclase activation Am J Physiol Heart Circ Physiol, June 1, 2008; 294(6): H2558 - H2564. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. C. Colombo, D. Onat, and H. N. Sabbah Acute heart failure as "acute endothelitis" -- Interaction of fluid overload and endothelial dysfunction Eur J Heart Fail, February 1, 2008; 10(2): 170 - 175. [Full Text] [PDF]
|
|
|
|
|
|
W.-Y. Lin, R. M. Levin, P. Chichester, R. Leggett, Y.-S. Juan, A. Johnson, P. Neumann, C. Whitbeck, A. Guven, B. Kogan, et al. Effects of L-arginine and L-NAME on chronic partial bladder outlet obstruction in rabbit Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2007; 293(6): R2390 - R2399. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. L. Sartorio, D. Fraccarollo, P. Galuppo, M. Leutke, G. Ertl, I. Stefanon, and J. Bauersachs Mineralocorticoid Receptor Blockade Improves Vasomotor Dysfunction and Vascular Oxidative Stress Early After Myocardial Infarction Hypertension, November 1, 2007; 50(5): 919 - 925. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Doerries, K. Grote, D. Hilfiker-Kleiner, M. Luchtefeld, A. Schaefer, S. M. Holland, S. Sorrentino, C. Manes, B. Schieffer, H. Drexler, et al. Critical Role of the NAD(P)H Oxidase Subunit p47phox for Left Ventricular Remodeling/Dysfunction and Survival After Myocardial Infarction Circ. Res., March 30, 2007; 100(6): 894 - 903. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Xu, R.H. Henning, E. Lipsic, A. van Buiten, W.H. van Gilst, and H. Buikema Acetylcholine stimulated dilatation and stretch induced myogenic constriction in mesenteric artery of rats with chronic heart failure Eur J Heart Fail, February 1, 2007; 9(2): 144 - 151. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Takimoto and D. A. Kass Role of Oxidative Stress in Cardiac Hypertrophy and Remodeling Hypertension, February 1, 2007; 49(2): 241 - 248. [Full Text] [PDF]
|
|
|
|
|
|
G. Csanyi, M. Bauer, W. Dietl, M. Lomnicka, T. Stepuro, B. K. Podesser, and S. Chlopicki Functional alterations in NO, PGI2 and EDHF pathways in the aortic endothelium after myocardial infarction in rats Eur J Heart Fail, December 1, 2006; 8(8): 769 - 776. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. M. Greer, A. K. Kakkar, J. W. Elrod, L. J. Watson, S. P. Jones, and D. J. Lefer Low-dose simvastatin improves survival and ventricular function via eNOS in congestive heart failure Am J Physiol Heart Circ Physiol, December 1, 2006; 291(6): H2743 - H2751. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. D. Searles Transcriptional and posttranscriptional regulation of endothelial nitric oxide synthase expression Am J Physiol Cell Physiol, November 1, 2006; 291(5): C803 - C816. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Hilfiker-Kleiner, U. Landmesser, and H. Drexler Molecular Mechanisms in Heart Failure: Focus on Cardiac Hypertrophy, Inflammation, Angiogenesis, and Apoptosis J. Am. Coll. Cardiol., October 27, 2006; 48(9_Suppl_A): A56 - A66. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Iida, Y. Chu, R. M. Weiss, Y. M. Kang, F. M. Faraci, and D. D. Heistad Vascular effects of a common gene variant of extracellular superoxide dismutase in heart failure Am J Physiol Heart Circ Physiol, August 1, 2006; 291(2): H914 - H920. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Bauersachs and D. Fraccarollo Endothelial NO Synthase Target of Aldosterone Hypertension, July 1, 2006; 48(1): 27 - 28. [Full Text] [PDF]
|
|
|
|
|
|
H. Post and B. Pieske Arginase: a modulator of myocardial function Am J Physiol Heart Circ Physiol, May 1, 2006; 290(5): H1747 - H1748. [Full Text] [PDF]
|
|
|
|
|
|
E. Ponsot, S. P. Dufour, J. Zoll, S. Doutrelau, B. N'Guessan, B. Geny, H. Hoppeler, E. Lampert, B. Mettauer, R. Ventura-Clapier, et al. Exercise training in normobaric hypoxia in endurance runners. II. Improvement of mitochondrial properties in skeletal muscle J Appl Physiol, April 1, 2006; 100(4): 1249 - 1257. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. D. Heistad Oxidative Stress and Vascular Disease: 2005 Duff Lecture Arterioscler Thromb Vasc Biol, April 1, 2006; 26(4): 689 - 695. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Thum, D. Fraccarollo, P. Galuppo, D. Tsikas, S. Frantz, G. Ertl, and J. Bauersachs Bone marrow molecular alterations after myocardial infarction: Impact on endothelial progenitor cells Cardiovasc Res, April 1, 2006; 70(1): 50 - 60. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Westendorp, R. G. Schoemaker, H. Buikema, F. Boomsma, D. J. van Veldhuisen, and W. H. van Gilst Progressive left ventricular hypertrophy after withdrawal of long-term ACE inhibition following experimental myocardial infarction Eur J Heart Fail, March 1, 2006; 8(2): 122 - 130. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. J. Guzik, J. Sadowski, B. Guzik, A. Jopek, B. Kapelak, P. Przybylowski, K. Wierzbicki, R. Korbut, D. G. Harrison, and K. M. Channon Coronary Artery Superoxide Production and Nox Isoform Expression in Human Coronary Artery Disease Arterioscler Thromb Vasc Biol, February 1, 2006; 26(2): 333 - 339. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Wang, S. Kramer, T. Loof, S. Martini, S. Kron, H. Kawachi, F. Shimizu, H.-H. Neumayer, and H. Peters Enhancing cGMP in experimental progressive renal fibrosis: soluble guanylate cyclase stimulation vs. phosphodiesterase inhibition Am J Physiol Renal Physiol, January 1, 2006; 290(1): F167 - F176. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Mollnau, M. Oelze, M. August, M. Wendt, A. Daiber, E. Schulz, S. Baldus, A. L. Kleschyov, A. Materne, P. Wenzel, et al. Mechanisms of Increased Vascular Superoxide Production in an Experimental Model of Idiopathic Dilated Cardiomyopathy Arterioscler Thromb Vasc Biol, December 1, 2005; 25(12): 2554 - 2559. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Chen, Y. Li, P. Zhang, J. H. Traverse, M. Hou, X. Xu, M. Kimoto, and R. J. Bache Dimethylarginine dimethylaminohydrolase and endothelial dysfunction in failing hearts Am J Physiol Heart Circ Physiol, November 1, 2005; 289(5): H2212 - H2219. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Begonja, S. Gambaryan, J. Geiger, B. Aktas, M. Pozgajova, B. Nieswandt, and U. Walter Platelet NAD(P)H-oxidase-generated ROS production regulates {alpha}IIb{beta}3-integrin activation independent of the NO/cGMP pathway Blood, October 15, 2005; 106(8): 2757 - 2760. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Kobayashi, F. A. DeLano, and G. W. Schmid-Schonbein Oxidative Stress Promotes Endothelial Cell Apoptosis and Loss of Microvessels in the Spontaneously Hypertensive Rats Arterioscler Thromb Vasc Biol, October 1, 2005; 25(10): 2114 - 2121. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-F. Lam and Z. S. Katusic Genetic modification of vascular endothelial function as therapeutic strategy in heart failure Am J Physiol Heart Circ Physiol, August 1, 2005; 289(2): H518 - H519. [Full Text] [PDF]
|
|
|
|
|
|
S. Iida, Y. Chu, J. Francis, R. M. Weiss, C. A. Gunnett, F. M. Faraci, and D. D. Heistad Gene transfer of extracellular superoxide dismutase improves endothelial function in rats with heart failure Am J Physiol Heart Circ Physiol, August 1, 2005; 289(2): H525 - H532. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Landmesser, F. Bahlmann, M. Mueller, S. Spiekermann, N. Kirchhoff, S. Schulz, C. Manes, D. Fischer, K. de Groot, D. Fliser, et al. Simvastatin Versus Ezetimibe: Pleiotropic and Lipid-Lowering Effects on Endothelial Function in Humans Circulation, May 10, 2005; 111(18): 2356 - 2363. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. B. Pereira, C. L. Sartorio, D. V. Vassallo, and I. Stefanon Differences in Tail Vascular Bed Reactivity in Rats with and without Heart Failure following Myocardial Infarction J. Pharmacol. Exp. Ther., March 1, 2005; 312(3): 1321 - 1325. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Bauersachs and A. Schafer Tetrahydrobiopterin and eNOS dimer/monomer ratio-a clue to eNOS uncoupling in diabetes? Cardiovasc Res, March 1, 2005; 65(4): 768 - 769. [Full Text] [PDF]
|
|
|
|
|
|
S. D. Katz, K. Hryniewicz, I. Hriljac, K. Balidemaj, C. Dimayuga, A. Hudaihed, and A. Yasskiy Vascular Endothelial Dysfunction and Mortality Risk in Patients With Chronic Heart Failure Circulation, January 25, 2005; 111(3): 310 - 314. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. C. Colombo, J. E. Banchs, S. Celaj, A. Talreja, J. Lachmann, S. Malla, N. B. DuBois, A. W. Ashton, F. Latif, U. P. Jorde, et al. Endothelial Cell Activation in Patients With Decompensated Heart Failure Circulation, January 4, 2005; 111(1): 58 - 62. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Chen, M. Hou, Y. Li, J. H. Traverse, P. Zhang, D. Salvemini, T. Fukai, and R. J. Bache Increased superoxide production causes coronary endothelial dysfunction and depressed oxygen consumption in the failing heart Am J Physiol Heart Circ Physiol, January 1, 2005; 288(1): H133 - H141. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-M. Li and A. M Shah Endothelial cell superoxide generation: regulation and relevance for cardiovascular pathophysiology Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2004; 287(5): R1014 - R1030. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Landmesser, N. Engberding, F. H. Bahlmann, A. Schaefer, A. Wiencke, A. Heineke, S. Spiekermann, D. Hilfiker-Kleiner, C. Templin, D. Kotlarz, et al. Statin-Induced Improvement of Endothelial Progenitor Cell Mobilization, Myocardial Neovascularization, Left Ventricular Function, and Survival After Experimental Myocardial Infarction Requires Endothelial Nitric Oxide Synthase Circulation, October 5, 2004; 110(14): 1933 - 1939. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Widder, T. Behr, D. Fraccarollo, K. Hu, P. Galuppo, P. Tas, C. E Angermann, G. Ertl, and J. Bauersachs Vascular endothelial dysfunction and superoxide anion production in heart failure are p38 MAP kinase-dependent Cardiovasc Res, July 1, 2004; 63(1): 161 - 167. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Schafer, D. Fraccarollo, P. Tas, I. Schmidt, G. Ertl, and J. Bauersachs Endothelial dysfunction in congestive heart failure: ACE inhibition vs. angiotensin II antagonism Eur J Heart Fail, March 1, 2004; 6(2): 151 - 159. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. J. Alp and K. M. Channon Regulation of Endothelial Nitric Oxide Synthase by Tetrahydrobiopterin in Vascular Disease Arterioscler Thromb Vasc Biol, March 1, 2004; 24(3): 413 - 420. [Abstract] [Full Text]
|
|
|
|
|
|
Y. Taniyama and K. K. Griendling Reactive Oxygen Species in the Vasculature: Molecular and Cellular Mechanisms Hypertension, December 1, 2003; 42(6): 1075 - 1081. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. G. Sharina, E. Martin, A. Thomas, K. L. Uray, and F. Murad CCAAT-binding factor regulates expression of the {beta}1 subunit of soluble guanylyl cyclase gene in the BE2 human neuroblastoma cell line PNAS, September 30, 2003; 100(20): 11523 - 11528. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Linz, G. Itter, L. W Dobrucki, T. Malinski, and G. Wiemer Ramipril improves nitric oxide availability in hypertensive rats with failing hearts after myocardial infarction Journal of Renin-Angiotensin-Aldosterone System, September 1, 2003; 4(3): 180 - 185. [Abstract] [PDF]
|
|
|
|
 |
|
 Y. Chen, S. Park, Y. Li, E. Missov, M. Hou, X. Han, J. L. Hall, L. W. Miller, and R. J. Bache Alterations of gene expression in failing myocardium following left ventricular assist device support Physiol Genomics, August 15, 2003; 14(3): 251 - 260. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Friebe and D. Koesling Regulation of Nitric Oxide-Sensitive Guanylyl Cyclase Circ. Res., July 25, 2003; 93(2): 96 - 105. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. G Harrison, Hua Cai, U. Landmesser, and K. K Griendling The Pickering Lecture British Hypertension Society, 10th September 2002: Interactions of angiotensin II with NAD(P)H oxidase, oxidant stress and cardiovascular disease Journal of Renin-Angiotensin-Aldosterone System, June 1, 2003; 4(2): 51 - 61. [Abstract] [PDF]
|
|
|
|
|
|
A. Schafer, D. Fraccarollo, S. K Hildemann, P. Tas, G. Ertl, and J. Bauersachs Addition of the selective aldosterone receptor antagonist eplerenone to ACE inhibition in heart failure: effect on endothelial dysfunction Cardiovasc Res, June 1, 2003; 58(3): 655 - 662. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. J. Dixon, D. R. Morgan, S. M. Hughes, L. T. McGrath, N. A. El-Sherbeeny, R. D. Plumb, A. Devine, W. Leahey, G. D. Johnston, and G. E. McVeigh Functional Consequences of Endothelial Nitric Oxide Synthase Uncoupling in Congestive Cardiac Failure Circulation, April 8, 2003; 107(13): 1725 - 1728. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Gschwend, H. Buikema, R. H. Henning, Y. M. Pinto, D. de Zeeuw, and W. H. van Gilst Endothelial dysfunction and infarct-size relate to impaired EDHF response in rat experimental chronic heart failure Eur J Heart Fail, March 1, 2003; 5(2): 147 - 154. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kloss, H. Furneaux, and A. Mulsch Post-transcriptional Regulation of Soluble Guanylyl Cyclase Expression in Rat Aorta J. Biol. Chem., January 17, 2003; 278(4): 2377 - 2383. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Landmesser, S. Spiekermann, S. Dikalov, H. Tatge, R. Wilke, C. Kohler, D. G. Harrison, B. Hornig, and H. Drexler Vascular Oxidative Stress and Endothelial Dysfunction in Patients With Chronic Heart Failure: Role of Xanthine-Oxidase and Extracellular Superoxide Dismutase Circulation, December 10, 2002; 106(24): 3073 - 3078. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Munzel, I. B. Afanas'ev, A. L. Kleschyov, and D. G. Harrison Detection of Superoxide in Vascular Tissue Arterioscler Thromb Vasc Biol, November 1, 2002; 22(11): 1761 - 1768. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P.a. Pacher, L. Liaudet, J. G. Mabley, K. Komjati, and C. Szabo Pharmacologic inhibition of poly(adenosine diphosphate-ribose) polymerase may represent a novel therapeutic approach in chronic heart failure J. Am. Coll. Cardiol., September 4, 2002; 40(5): 1006 - 1016. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Christ, J. Bauersachs, C. Liebetrau, M. Heck, A. Gunther, and M. Wehling Glucose Increases Endothelial-Dependent Superoxide Formation in Coronary Arteries by NAD(P)H Oxidase Activation: Attenuation by the 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitor Atorvastatin Diabetes, August 1, 2002; 51(8): 2648 - 2652. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Fukuo, J. Yang, O. Yasuda, M. Mogi, T. Suhara, N. Sato, T. Suzuki, S. Morimoto, and T. Ogihara Nifedipine Indirectly Upregulates Superoxide Dismutase Expression in Endothelial Cells via Vascular Smooth Muscle Cell-Dependent Pathways Circulation, July 16, 2002; 106(3): 356 - 361. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Landmesser and H. Drexler Allopurinol and Endothelial Function in Heart Failure: Future or Fantasy? Circulation, July 9, 2002; 106(2): 173 - 175. [Full Text] [PDF]
|
|
|
|
|
|
J. H. Traverse, Y. Chen, M. Hou, and R. J. Bache Inhibition of NO production increases myocardial blood flow and oxygen consumption in congestive heart failure Am J Physiol Heart Circ Physiol, June 1, 2002; 282(6): H2278 - H2283. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ahmad, Y. Zhang, Y. Zhang, C. Papharalambus, and R. W. Alexander Role of Isoprenylcysteine Carboxyl Methyltransferase in Tumor Necrosis Factor-{alpha} Stimulation of Expression of Vascular Cell Adhesion Molecule-1 in Endothelial Cells Arterioscler Thromb Vasc Biol, May 1, 2002; 22(5): 759 - 764. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Sanchez de Miguel, M. a M. Arriero, J. Farre, P. Jimenez, A. Garcia-Mendez, T. de Frutos, A. Jimenez, R. Garcia, F. Cabestrero, J. Gomez, et al. Nitric oxide production by neutrophils obtained from patients during acute coronary syndromes: expression of the nitric oxide synthase isoforms J. Am. Coll. Cardiol., March 6, 2002; 39(5): 818 - 825. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Bauersachs, M. Heck, D. Fraccarollo, S. K. Hildemann, G. Ertl, M. Wehling, and M. Christ Addition of spironolactone to angiotensin-converting enzyme inhibition in heart failure improves endothelial vasomotor dysfunction: Role of vascular superoxide anion formation and endothelial nitric oxide synthase expression J. Am. Coll. Cardiol., January 16, 2002; 39(2): 351 - 358. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Wagner, K. Hu, J. Bauersachs, J. Karcher, M. Wiesler, S. K. Goparaju, G. Kunos, and G. Ertl Endogenous cannabinoids mediate hypotension after experimental myocardial infarction J. Am. Coll. Cardiol., December 1, 2001; 38(7): 2048 - 2054. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. de Lorgeril, P. Salen, M. Accominotti, M. Cadau, J.-P. Steghens, F. Boucher, and J. de Leiris Dietary and blood antioxidants in patients with chronic heart failure. Insights into the potential importance of selenium in heart failure Eur J Heart Fail, December 1, 2001; 3(6): 661 - 669. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Marques, I. Millas, A. Jimenez, E. Garcia-Colis, J. A. Rodriguez-Feo, S. Velasco, A. Barrientos, S. Casado, and A. Lopez-Farre Alteration of the Soluble Guanylate Cyclase System in the Vascular Wall of Lead-Induced Hypertension in Rats J. Am. Soc. Nephrol., December 1, 2001; 12(12): 2594 - 2600. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Nakamura, K. Egashira, K. Arimura, Y. Machida, T. Ide, H. Tsutsui, H. Shimokawa, and A. Takeshita Increased inactivation of nitric oxide is involved in impaired coronary flow reserve in heart failure Am J Physiol Heart Circ Physiol, December 1, 2001; 281(6): H2619 - H2625. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Wiemer, G. Itter, T. Malinski, and W. Linz Decreased Nitric Oxide Availability in Normotensive and Hypertensive Rats With Failing Hearts After Myocardial Infarction Hypertension, December 1, 2001; 38(6): 1367 - 1371. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. F. Mitchell, J.-C. Tardif, J. M. O. Arnold, G. Marchiori, T. X. O'Brien, M. E. Dunlap, and M. A. Pfeffer Pulsatile Hemodynamics in Congestive Heart Failure Hypertension, December 1, 2001; 38(6): 1433 - 1439. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Wildhirt, M. Weis, C. Schulze, N. Conrad, S. Pehlivanli, G. Rieder, G. Enders, W. von Scheidt, and B. Reichart Expression of Endomyocardial Nitric Oxide Synthase and Coronary Endothelial Function in Human Cardiac Allografts Circulation, September 18, 2001; 104 (2009): I-336 - I-343. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Bauersachs, I. Fleming, D. Fraccarollo, R. Busse, and G. Ertl Prevention of endothelial dysfunction in heart failure by vitamin E: Attenuation of vascular superoxide anion formation and increase in soluble guanylyl cyclase expression Cardiovasc Res, August 1, 2001; 51(2): 344 - 350. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. V. Ennezat, S. L. Malendowicz, M. Testa, P. C. Colombo, A. Cohen-Solal, T. Evans, and T. H. LeJemtel Physical training in patients with chronic heart failure enhances the expression of genes encoding antioxidative enzymes J. Am. Coll. Cardiol., July 1, 2001; 38(1): 194 - 198. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Wildhirt, M. Weis, C. Schulze, N. Conrad, S. Pehlivanli, G. Rieder, G. Enders, W. von Scheidt, and B. Reichart Coronary flow reserve and nitric oxide synthases after cardiac transplantation in humans Eur. J. Cardiothorac. Surg., June 1, 2001; 19(6): 840 - 847. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Mulsch, M. Oelze, S. Kloss, H. Mollnau, A. Topfer, A. Smolenski, U. Walter, J.-P. Stasch, A. Warnholtz, U. Hink, et al. Effects of In Vivo Nitroglycerin Treatment on Activity and Expression of the Guanylyl Cyclase and cGMP-Dependent Protein Kinase and Their Downstream Target Vasodilator-Stimulated Phosphoprotein in Aorta Circulation, May 1, 2001; 103(17): 2188 - 2194. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. J Wagenaar, H. Buikema, Y. M Pinto, and W. H van Gilst Improvement of endothelial dysfunction in experimental heart failure by chronic RAAS-blockade: ACE-inhibition or AT1-receptor blockade? Journal of Renin-Angiotensin-Aldosterone System, March 1, 2001; 2(1_suppl): S64 - S69. [Abstract] [PDF]
|
|
|
|
|
|
A.C. Mendes Ribeiro, T.M.C. Brunini, J.C. Ellory, and G.E. Mann Abnormalities in L-arginine transport and nitric oxide biosynthesis in chronic renal and heart failure Cardiovasc Res, March 1, 2001; 49(4): 697 - 712. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Cai and D. G. Harrison Endothelial Dysfunction in Cardiovascular Diseases: The Role of Oxidant Stress Circ. Res., November 10, 2000; 87(10): 840 - 844. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. M. Channon, H. Qian, and S. E. George Nitric Oxide Synthase in Atherosclerosis and Vascular Injury : Insights From Experimental Gene Therapy Arterioscler Thromb Vasc Biol, August 1, 2000; 20(8): 1873 - 1881. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Bauersachs, D. Fraccarollo, P. Galuppo, J. Widder, and G. Ertl Endothelin-receptor blockade improves endothelial vasomotor dysfunction in heart failure Cardiovasc Res, July 1, 2000; 47(1): 142 - 149. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. B. Driss, C. Devaux, D. Henrion, M. Duriez, C. Thuillez, B. I. Levy, and J.-B. Michel Hemodynamic Stresses Induce Endothelial Dysfunction and Remodeling of Pulmonary Artery in Experimental Compensated Heart Failure Circulation, June 13, 2000; 101(23): 2764 - 2770. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. J. Guzik, N. E. J. West, E. Black, D. McDonald, C. Ratnatunga, R. Pillai, and K. M. Channon Vascular Superoxide Production by NAD(P)H Oxidase : Association With Endothelial Dysfunction and Clinical Risk Factors Circ. Res., May 12, 2000; 86 (9): e85 - e90. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. P. Brandes, D.-y. Kim, F.-H. Schmitz-Winnenthal, M. Amidi, A. Godecke, A. Mulsch, and R. Busse Increased Nitrovasodilator Sensitivity in Endothelial Nitric Oxide Synthase Knockout Mice : Role of Soluble Guanylyl Cyclase Hypertension, January 1, 2000; 35(1): 231 - 236. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Munzel and D. G. Harrison Increased Superoxide in Heart Failure : A Biochemical Baroreflex Gone Awry Circulation, July 20, 1999; 100(3): 216 - 218. [Full Text] [PDF]
|
|
|
|
|
|
H.-Y. Sohn, M. Keller, T. Gloe, H. Morawietz, U. Rueckschloss, and U. Pohl The Small G-protein Rac Mediates Depolarization-induced Superoxide Formation in Human Endothelial Cells J. Biol. Chem., June 16, 2000; 275(25): 18745 - 18750. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. B. Haitsma, D. Merkus, J. Vermeulen, P. D. Verdouw, and D. J. Duncker Nitric oxide production is maintained in exercising swine with chronic left ventricular dysfunction Am J Physiol Heart Circ Physiol, June 1, 2002; 282(6): H2198 - H2209. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. D. Thomas, W. Zhang, and R. G. Victor Impaired Modulation of Sympathetic Vasoconstriction in Contracting Skeletal Muscle of Rats With Chronic Myocardial Infarctions : Role of Oxidative Stress Circ. Res., April 27, 2001; 88(8): 816 - 823. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||