(Circulation. 2000;101:1722.)
© 2000 American Heart Association, Inc.
Basic Science Reports |
Vascular Superoxide Production and Vasomotor Function in Hypertension Induced by Deoxycorticosterone Acetate–Salt
From the Division of Cardiology, Emory University School of Medicine and Atlanta VA Hospital, Atlanta, Ga.
Correspondence to David G. Harrison, MD, 319 WMRB, 1639 Pierce Dr, Atlanta, GA 30322. E-mail dharr02{at}emory.edu
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
Background—Angiotensin II–induced hypertension is associated with increased vascular superoxide production, which contributes to hypertension caused by the octapeptide. In cell culture, stretch increases endothelial and vascular smooth muscle production of reactive oxygen species (ROS). In perfused isolated vessels, elevations of pressure can increase vessel angiotensin II production. The effects of low-renin hypertension on vascular ROS production remain unclear. Furthermore, the role of ROS in vascular function and hypertension in low-renin hypertension is undefined.
Methods and Results—Rats were treated with DOCA and saline drinking water for 3 weeks. Both systolic blood pressure (189±4 versus 126±2 mm Hg) and aortic superoxide production (3972±257 versus 852±287, P<0.05) were increased compared with controls. Relaxations of vascular segments to acetylcholine (ACh, 100±2% versus 75±2%, P<0.05) and the calcium ionophore A23187 (92±2% versus 72±3%, P<0.05) were also impaired in DOCA-salt. Heparin-binding superoxide dismutase (1200 U/d IV for 3 days) had no effect on blood pressure but significantly improved relaxations to ACh and A23187. Losartan (25 mg · kg-1 · d-1 PO) for 7 days did not correct the hypertension or endothelium-dependent vessel relaxation in DOCA-salt rats, excluding a role of a local renin/angiotensin II system.
Conclusions—These findings indicate that increased vascular superoxide production occurs not only in angiotensin II–induced hypertension but also in hypertension known to be associated with low-renin states. Increased superoxide production alters large-vessel endothelium-dependent vascular relaxation but does not modulate blood pressure in low-renin hypertension.
Key Words: hypertension • angiotensin • free radicals • endothelium
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
The production of reactive oxygen species by vascular cells seems to play a critical role in the genesis of vascular disease. Recently, it has become clear that angiotensin II can dramatically increase the activity of an NADH/NADPH-driven oxidase, a major source of reactive oxygen species in vascular cells.1 2 3 In rats, angiotensin II–induced hypertension is associated with an increase in vascular superoxide production, which in turn seems to reduce the biological activity of endothelium-derived nitric oxide (NO).3 This loss of NO bioactivity dramatically alters vascular reactivity and contributes to elevations of blood pressure caused by angiotensin II.4 Increased production of hydrogen peroxide in response to angiotensin II seems to be critical in the development of vascular smooth muscle hypertrophy caused by the peptide.5
In previous studies, we have shown that short-term hypertension (5 days) caused by norepinephrine, unlike that caused by angiotensin II, was not associated with an increase in vascular production of superoxide and did not alter vascular reactivity.3 These findings suggested that angiotensin II may be unique as a cause of vascular oxidant stress, whereas other causes of hypertension may not have this effect on vascular function. This conclusion was supported by the observation that lower-dose administration of angiotensin II, not associated with an increase in blood pressure, also increased vascular superoxide production. An important caveat is that the lack of effect of norepinephrine on vascular superoxide production was observed during a relatively short term (5 days) of hypertension. Furthermore, hypertension caused by norepinephrine is unique in that it is associated with an increase in cardiac output and ultimately an increase in vascular shear stress, which may have independent effects on vascular function.
In contrast to the above-described findings, recent studies have shown that stretch of vascular cells can enhance production of both superoxide and H2O2.6 7 8 These findings raise the possibility that the direct effects of hypertension, which directly increases stretch of vascular smooth muscle cells in vivo, might also increase vascular production of reactive oxygen species. To examine this, we studied rats with deoxycorticosterone acetate (DOCA)-salt hypertension. This model of hypertension is associated with markedly depressed plasma renin activity9 and thus provides an opportunity to study the effect of hypertension in the absence of angiotensin II on vascular superoxide production and vascular reactivity.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Materials
Deoxycorticosterone acetate (DOCA) pellets and control pellets were purchased from Innovative Research of America. Heparin was purchased from Upjohn Corp. Pentobarbital and ketamine were purchased from Abbot Laboratories. Xylazine was purchased from Bayer. Nitroglycerin was purchased from American Regent Laboratories. Losartan was provided as a gift from Merck. Heparin-binding superoxide dismutase (HB-SOD) was provided by Dr Margaret Tarpey, Birmingham, Ala. Dihydroethidium was purchased from Molecular Probes. All other chemicals were purchased from Sigma-Aldrich.
DOCA-Salt Rats
Male Sprague-Dawley Rats (250 to 300 g, Harlan Sprague
Dawley Inc, Indianapolis, Ind) were anesthetized with
intraperitoneal ketamine (80 mg/kg) and
xylazine (10 mg/kg). A midscapular incision was made, and a 100-mg
slow-release DOCA pellet was inserted subcutaneously. A right flank
incision was made and a right nephrectomy performed. Drinking water was
replaced by 1% saline. Control rats underwent nephrectomy and
implantation with a sham pellet and were given water ad libitum. A
separate group of rats underwent DOCA pellet implantation alone without
saline to determine the direct effects of DOCA on
endothelial function. On day 16, the rats were
acclimated 1 hour in the plethysmography unit. On day 21 after
operation, blood pressures were measured by tail-cuff plethysmography,
and the rats were euthanized with intraperitoneal
sodium pentobarbital.
In some experiments, rats were treated with HB-SOD. HB-SOD is a recombinant form of SOD that accumulates in the vascular extracellular matrix and potently scavenges O2·- produced by vascular cells.2 The rats were anesthetized on day 15 after DOCA pellet implantation, and a Tygon catheter was implanted in the left carotid artery with the tip advanced to the ascending aorta. A second catheter was implanted into the left jugular vein. The catheters were externalized through a second incision and plugged with a nylon pin. On days 18 to 21, the rats underwent intravenous injection with 600 U/kg of HB-SOD every 12 hours. On the day of death, the blood pressure was monitored with the aortic catheter connected to a Gould pressure transducer and an oscillographic recorder (Gould RS3600). The rats were then killed with sodium pentobarbital.
AT1 Receptor Antagonist Studies
In some rats, on day 10 to 21 after pellet implantation, the
rats were given 25 mg · kg-1 ·
d-1 of the specific angiotensin II
receptor type 1 antagonist losartan in their
drinking fluid.
Vessel Preparation
The aorta was placed into chilled modified Krebs/HEPES buffer
(composition in mmol/L: NaCl 99.01, KCl 4.69,
CaCl2 1.87, MgSO4 1.20,
K2HPO4 1.03,
NaHCO3 25.0, Na-HEPES 20.0, and glucose 11.1; pH
7.4), cleaned of excessive adventitial tissue, and cut into 5-mm ring
segments, with care taken not to injure the
endothelium.
Estimation of Vascular O2·-
Production
Superoxide production was measured by lucigenin
chemiluminescence. The details of this method have been published
previously.10 11 12 Recently, 5 µmol/L lucigenin has
been shown to correlate well with electron spin resonance as a
quantitative measurement of superoxide
production.13 14 15 Briefly, after preparation, the
vessels were placed in a modified Krebs/HEPES buffer and allowed to
equilibrate for 30 minutes at 37°C. Scintillation vials containing 2
mL Krebs/HEPES buffer with 5 µmol/L lucigenin were placed into a
scintillation counter switched to out-of-coincidence mode. After dark
adaptation, background counts were recorded, and a vascular segment
was added to the vial. Scintillation counts were then recorded
every minute, and the counts from 15 to 19 minutes were averaged
(steady-state production). The vessels were then dried in an
oven at 90°C for 24 hours, and the counts were expressed as counts
above background per milligram dry tissue.
Additional studies were performed with in situ dihydroethidium fluorescence as described previously.16 Three frozen 30-µm tissue sections from each of 3 matched pairs of DOCA-salt and control rat aortas were placed on glass slides. The sections were submerged in 2 µmol/L dihydroethidium in Krebs/HEPES buffer and incubated at 37°C for 30 minutes in a dark, humidified container. Tissue sections were then visualized with a Bio-Rad MRC 1024 argon confocal microscope with fluorescence detected with a 585-nm long-pass filter, and images were collected and stored digitally. Paired aortas from DOCA-salt and control rats were processed in parallel, and images were acquired with identical acquisition parameters.
Isolated Vascular Ring Experiments
Four 5-mm ring segments of the thoracic aorta were suspended in
individual organ chambers filled with Krebs buffer of the following
composition (mmol/L): NaCl 99.01, KCl 4.69, CaCl2
1.87, MgSO4 1.20,
K2HPO4 1.03,
NaHCO3 25.0, and glucose 11.1; pH 7.4. The
solution was aerated continuously with a 95%
O2/5% CO2 mixture and
maintained at 37°C. Care was taken not to injure the
endothelium during preparation of the rings. Tension
was recorded with a linear force transducer. Over a period of 1
hour, the resting tension was gradually increased until the optimal
tension for generating force during isometric contraction was achieved;
this proved to be 4.0 g in all subsets of animals. The vessels
were left at this resting tension throughout the remainder of the
study. To prevent synthesis of prostaglandins, we performed
all experiments in the presence of 10 µmol/L
indomethacin. The vessels were then precontracted with
L-phenylephrine (10-7
mol/L). After a stable contraction plateau was reached, the rings were
exposed to either acetylcholine (1 nmol/L to 3 µmol/L), the
calcium ionophore (1 nm to 3 µmol/L), or
nitroglycerin (1 nm to 3 µmol/L).
Data Analysis
Data are expressed as mean±SEM. Comparisons between groups of
animals or treatments were made by 1-way ANOVA. When significance was
indicated, a Student-Newman-Keuls post hoc analysis was
used.
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Effects of DOCA-Salt on Blood Pressure and Vascular Superoxide Production
Treatment with DOCA-salt caused a significant increase in systolic blood pressure after 21 days, from 126±2 mm Hg in sham-operated rats to 189±4 mm Hg in DOCA-salt–treated rats (Figure 1A
). The amount of superoxide
measured by lucigenin chemiluminescence was significantly higher in
aortas from DOCA-salt rats (3972±257 counts ·
mg-1 ·
min-1) than that in aortas from
sham-operated animals (852±287 counts ·
mg-1 · min-1)
(Figure 1B).
|
To examine vascular O2·-
production by an independent approach and to gain insight into
the vascular localization of
O2·- production, we
also used dihydroethidium fluorescent staining. Aortas of
DOCA-salt rats consistently showed increased red
fluorescence, indicating increased superoxide levels, compared
with controls (n=3 pairs of DOCA-salt and sham-operated rats, Figure 2). Of note, dihydroethidium
fluorescence was increased in all cell layers of vessels from
DOCA-salt rats compared with controls.
|
Effects of DOCA-Salt on Vascular Relaxation
As shown in Figure 3 and the
Table, DOCA-salt produced
significant impairment in endothelium-dependent and
-independent vascular relaxations. The maximum relaxation induced by
acetylcholine, calcium ionophore A23187, and
nitroglycerin was all significantly reduced.
Sensitivity to acetylcholine, as reflected by the
EC50, was also reduced.
|
|
Role of Superoxide in Hypertension and Vascular Relaxations in
DOCA-Salt Hypertension
The above-cited data show that DOCA-salt hypertension is
associated with an increase in vascular
O2·- production and
altered endothelium-dependent vascular relaxations. In
angiotensin II–induced hypertension, both hypertension and
altered endothelium-dependent vascular relaxation can
be improved by treatment with membrane-targeted forms of superoxide
dismutase (SOD).3 4 We therefore examined the role of
increased vascular O2·- in
hypertension and altered endothelium-dependent vascular
relaxation in DOCA-salt hypertension. Treatment with heparin-binding
SOD did not significantly decrease the blood pressure in rats with
DOCA-salt hypertension (189±4 mm Hg without SOD versus
195±3 mm Hg with SOD) (Figure 4).
Treatment with heparin-binding SOD significantly improved
endothelium-dependent vascular relaxations to A23187
and acetylcholine in DOCA-salt–treated rats compared with similar
responses in DOCA-salt rats not treated with SOD (Figure 5 and Table
).
|
|
Role of a Local Renin-Angiotensin System in
DOCA-Salt Hypertension
It has been shown in an ex vivo animal model that perfusion of
vessels at hypertensive pressures activates production
of angiotensin II by a local renin-angiotensin
system.17 Furthermore, angiotensin
II increases production of reactive oxygen species by
vascular smooth muscle cells in both cultured cells and intact vessels.
Thus, it is possible that increased local levels of
angiotensin II produced in the vessel wall might mediate
the increase in vascular O2·-
observed in DOCA-salt hypertension. As shown in Figure 6, however, losartan did not
alter blood pressure or endothelium-dependent vascular
relaxation in rats with DOCA-salt hypertension.
|
Effect of DOCA Alone on Superoxide, Pressure, and Vascular
Relaxation
DOCA-salt may increase vascular superoxide production by a
direct mineralocorticoid effect rather than stretch. To investigate
this possibility, a separate group of rats were implanted with a DOCA
pellet and given water ad libitum. No significant changes were seen in
blood pressure, vascular O2·-
production, or vascular relaxation compared with placebo.
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
The new findings in this study are that in DOCA-salt hypertension, there is an increase in vascular O2·- production that at least in part contributes to alterations of endothelium-dependent vascular relaxation. This increase in O2·- production occurs in a model of hypertension known to be associated with suppression of the systemic renin-angiotensin system, suggesting that it was independent of locally produced angiotensin II. Furthermore, unlike the effect on endothelium-dependent vascular relaxation, the reducing vascular O2·- production did not ameliorate the hypertension caused by DOCA-salt.
In previous studies, we found that hypertension caused by angiotensin II markedly increased vascular O2·- production, which in turn diminished endothelium-dependent vascular relaxation and contributed to the elevation of blood pressure caused by the octapeptide.3 4 These properties were not shared by norepinephrine-induced hypertension, suggesting that angiotensin II–induced hypertension may have unique untoward effects on vascular function. These previous studies compared hypertension caused by rather short-term (5-day) infusions of angiotensin II or norepinephrine but did not address the possibility that longer-term hypertension of any cause might also increase vascular production of reactive oxygen species. The present studies show that long-term hypertension, in the presence of a suppressed renin-angiotensin system, can also dramatically increase vascular production of O2·-.
The increase in vascular O2·- production detected by lucigenin-enhanced chemiluminescence was confirmed by in situ dihydroethidium staining. Oxidation of dihydroethidium to ethidium, as detected by this fluorescent technique, has been shown to be specific for O2·-.18 Interestingly, fluorescence was particularly increased in endothelial and adventitial cells but was also increased in vascular smooth muscle cells of DOCA-salt rats compared with paired images of sham-treated rats. The mechanisms and enzyme systems responsible for increased O2·- production in these various cell layers remain unidentified and may vary. A major source of vascular O2·- production has been shown to be an NADH/NADPH oxidase.19 20 In cultured cells, this oxidase is activated by cyclic stretch,8 and it is conceivable that the direct mechanical effect of hypertension on the vessel wall has a similar effect in vivo. It has recently been shown that all of the components of the neutrophil NADPH oxidase exist in endothelial and adventitial cells.21 22 In contrast, only p22phox and p47phox have been definitively identified in vascular smooth muscle cells to date.23 24 Other enzyme systems may also be involved, including NO synthase, which can produce O2·- in the absence of either L-arginine or tetrahydrobiopterin.25 26
Our findings are compatible with previous studies showing that endothelium-dependent vascular relaxations are altered in both conductance and resistance vessels in DOCA-salt hypertension.27 The present findings add to these previous studies by showing that this abnormality of vascular function is in part caused by an increase in vascular O2·-, because these responses were improved by treatment with heparin-binding SOD. In rat aorta, the major endothelium-derived relaxing factor is NO, which rapidly reacts with O2·- to form the peroxynitrite anion.28 The fact that SOD improved these responses is consistent with a role of O2·- in alteration of NO bioavailability. Interestingly, responses to nitroglycerin were improved by treatment with heparin-binding (HB)-SOD in sham-treated but not in DOCA-salt rats. This may be related to the sites of nitroglycerin bioconversion, the location at which the HB-SOD accumulates, and the site of O2·- production in vessels of sham-treated and DOCA-salt rats.
Treatment with heparin-binding SOD failed to lower blood pressure in rats with DOCA-salt hypertension. This is in contrast to the effect of membrane-targeted forms of SOD and other antioxidants on blood pressure in angiotensin II–induced hypertension and in spontaneously hypertensive rats.3 29 30 The reasons for these differences remain unclear. DOCA-salt hypertension is largely mediated by increased intravascular volume and circulating catecholamines, factors that are most likely independent of vascular superoxide production. Indeed, Huang et al31 32 showed that the severity of hypertension in the DOCA-salt model is relatively independent of systemic vascular resistance. In these previous studies, the potent vasodilator minoxidil lowered systemic vascular resistance by 20% but did not alter blood pressure in rats with DOCA-salt hypertension. Thus, even if the bioactivity of NO in the resistance circulation were to be improved by heparin-binding SOD, this might not affect blood pressure in DOCA-salt hypertension.
It has recently been shown that ex vivo perfusion of vessels at hypertensive pressures activates production of angiotensin II by a local renin-angiotensin system.17 Consequently, it is possible that locally produced angiotensin II, even in the absence of increased plasma angiotensin II, might have contributed to the increase in vascular O2·- production in DOCA-salt hypertension. To exclude a role of local angiotensin II, some animals were treated with the AT1 receptor antagonist losartan. Blockade of this angiotensin II receptor failed to block the effects of DOCA-salt on blood pressure or vascular relaxation. These data exclude the role of a local renin–angiotensin II system in the effects of DOCA-salt on vascular reactivity.
Although these studies show that the vascular production of reactive oxygen species is increased by chronic hypertension in the absence of an elevation of angiotensin II, they do not discount an important role of angiotensin II in conditions in which it is elevated. Angiotensin II activates the NADH/NADPH oxidase in vascular smooth muscle cells both in culture1 and when infused in vivo in low concentrations that only minimally affect blood pressure.3 Recent studies suggest that locally produced angiotensin II may increase vascular O2·- production in atherosclerotic vessels in the absence of an increase in blood pressure.13 33 Taken together with our present findings, these data strongly suggest that hypertension per se can increase vascular production of reactive oxygen species but that angiotensin II can produce this effect via 2 mechanisms. These include a direct action of the octapeptide on vascular smooth muscle cells and an increase in blood pressure, which in turn stimulates vascular production of reactive oxygen species.
In summary, the present studies show that hypertension associated
with low levels of angiotensin II can increase in vascular
O2·- production,
which in turn reduces the bioactivity of
endothelium-derived NO. In light of previous studies of
renovascular hypertension,34 genetic
hypertension,29 30 35 and hypertension caused by exogenous
angiotensin II,2 3 4 these studies suggest that
hypertension of almost any cause can increase vascular oxidant stress.
An important aspect of this phenomenon is a reduction of NO
bioactivity. NO has several effects on vascular homeostasis that
inhibit the atherogenic process. These include inhibition of expression
of the vascular cell adhesion molecule-136 and the
monocyte chemoattractant protein-1,37 suppression of
nuclear factor-
B activation,38 and inhibition of
platelet adhesion and vascular smooth muscle cell proliferation.
Loss of these effects via an increase in vascular
O2·- production could
contribute to the proatherogenic effect of hypertension and emphasizes
the importance of blood pressure lowering to minimize the development
of vascular disease.
|
Acknowledgments |
|---|
This work was supported by NIH RO-1s HL-39006, HL-59248, program project HL-58000, and a Veterans Administration Merit Grant. Dr Somers was supported in part by the Cardiofellows Foundation.
Received July 8, 1999; revision received October 20, 1999; accepted November 2, 1999.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
1. Griendling KK, Ollerenshaw JD, Minieri CA, Alexander RW. Angiotensin II stimulates NADH and NADPH activity in cultured vascular smooth muscle cells. Circ Res. 1994;74:1141–1148.
2.
Fukui T, Ishizaka N, Rajagopalan S, Laursen JB, Capers
QT, Taylor WR, Harrison DG, de Leon H, Wilcox JN, Griendling KK.
p22phox mRNA expression and NADPH oxidase activity are increased in
aortas from hypertensive rats. Circ Res. 1997;80:45–51.
3. 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: contribution to alterations of vasomotor tone. J Clin Invest. 1996;97:1916–1923.[Medline] [Order article via Infotrieve]
4.
Bech Laursen J, Rajagopalan S, Tarpey M, Freeman BA,
Harrison DG. A role of superoxide in angiotensin II but not
catecholamine-induced hypertension. Circulation. 1997;95:588–593.
5.
Zafari AM, Ushio-Fukai M, Akers M, Yin Q, Shah A,
Harrison DG, Taylor WR, Griendling KK. Role of NADH/NADPH
oxidase-derived H2O2 in
angiotensin II–induced vascular hypertrophy.
Hypertension. 1998;32:488–495.
6.
Hishikawa K, Luscher TF. Pulsatile stretch stimulates
superoxide production in human aortic
endothelial cells. Circulation. 1997;96:3610–3616.
7.
Hishikawa K, Oemar BS, Yang Z, Luscher TF. Pulsatile
stretch stimulates superoxide production and activates
nuclear factor-B in human coronary smooth muscle.
Circ Res. 1997;81:797–803.
8.
Howard AB, Alexander RW, Nerem RM, Griendling KK,
Taylor WR. Cyclic strain induces an oxidative stress in
endothelial cells. Am J Physiol. 1997;272:C421–C427.
9.
Gavras H, Brunner HR, Laragh JH, Vaughan ED Jr, Koss
M, Cote LJ, Gavras I. Malignant hypertension resulting from
deoxycorticosterone acetate and salt excess: role of renin and sodium
in vascular changes. Circ Res. 1975;36:300–309.
10. Ohara Y, Peterson TE, Harrison DG. Hypercholesterolemia increases endothelial superoxide anion production. J Clin Invest. 1993;91:2546–2551.
11.
Ohara Y, Peterson TE, Sayegh HS, Subramanian RR, Wilcox
JN, Harrison DG. Dietary correction of
hypercholesterolemia in the rabbit normalizes
endothelial superoxide anion production.
Circulation. 1995;92:898–903.
12. Munzel T, Sayegh H, Freeman BA, Tarpey MM, Harrison DG. Evidence for enhanced vascular superoxide anion production in nitrate tolerance: a novel mechanism underlying tolerance and cross-tolerance. J Clin Invest. 1995;95:187–194.
13.
Warnholtz A, Nickenig G, Schulz E, Macharzina R, Brasen
JH, Skatchkov M, Heitzer T, Stasch JP, Griendling KK, Harrison DG, Bohm
M, Meinertz T, Munzel T. Increased NADH-oxidase–mediated superoxide
production in the early stages of
atherosclerosis: evidence for involvement of the
renin-angiotensin system. Circulation. 1999;99:2027–2033.
14. Skatchkov MP, Sperling D, Hink U, Mulsch A, Harrison DG, Sindermann I, Meinertz T, Munzel T. Validation of lucigenin as a chemiluminescent probe to monitor vascular superoxide as well as basal vascular nitric oxide production. Biochem Biophys Res Commun. 1999;254:319–324.[Medline] [Order article via Infotrieve]
15.
Li Y, Zhu H, Kuppusamy P, Roubaud V, Zweier JL, Trush
MA. Validation of lucigenin (bis-N-methylacridinium) as a
chemilumigenic probe for detecting superoxide anion radical
production by enzymatic and cellular systems. J Biol
Chem. 1998;273:2015–2023.
16.
Miller FJ Jr, Gutterman DD, Rios CD, Heistad DD,
Davidson BL. Superoxide production in vascular smooth muscle
contributes to oxidative stress and impaired relaxation in
atherosclerosis. Circ Res. 1998;82:1298–1305.
17.
Bardy N, Merval R, Benessiano J, Samuel JL, Tedgui A.
Pressure and angiotensin II synergistically induce aortic
fibronectin expression in organ culture model of rabbit aorta: evidence
for a pressure-induced tissue renin-angiotensin system.
Circ Res. 1996;79:70–78.
18.
Bindokas VP, Jordan J, Lee CC, Miller RJ. Superoxide
production in rat hippocampal neurons: selective imaging with
hydroethidine. J Neurosci. 1996;16:1324–1336.
19.
Mohazzab KM, Kaminski PM, Wolin MS. NADH oxidoreductase
is a major source of superoxide anion in bovine coronary artery
endothelium. Am J Physiol. 1994;266:H2568–H2572.
20.
Pagano P, Ito Y, Tornheim K, Gallop P, Tauber A, Cohen
R. An NADPH oxidase superoxide-generating system in the rabbit aorta.
Am J Physiol. 1995;268:H2274–H2280.
21. Jones SA, Hancock JT, Jones OT, Neubauer A, Topley N. The expression of NADPH oxidase components in human glomerular mesangial cells: detection of protein and mRNA for p47phox, p67phox, and p22phox. J Am Soc Nephrol. 1995;5:1483–1491.[Abstract]
22.
Wang HD, Pagano PJ, Du Y, Cayatte AJ, Quinn MT, Brecher
P, Cohen RA. Superoxide anion from the adventitia of the rat thoracic
aorta inactivates nitric oxide. Circ Res. 1998;82:810–818.
23.
Patterson C, Ruef J, Madamanchi NR, Barry-Lane P, Hu Z,
Horaist C, Ballinger CA, Brasier AR, Bode C, Runge MS. Stimulation of a
vascular smooth muscle cell NAD(P)H oxidase by thrombin: evidence that
p47(phox) may participate in forming this oxidase in vitro and in vivo.
J Biol Chem. 1999;274:19814–19822.
24.
Ushio-Fukai M, Zafari AM, Fukui T, Ishizaka N,
Griendling KK. p22phox is a critical component of the
superoxide-generating NADH/NADPH oxidase system and regulates
angiotensin II-induced hypertrophy in vascular
smooth muscle cells. J Biol Chem. 1996;271:23317–23321.
25.
Xia Y, Tsai AL, Berka V, Zweier JL. Superoxide
generation from endothelial nitric-oxide synthase: a
Ca2+/calmodulin-dependent and
tetrahydrobiopterin regulatory process. J Biol Chem. 1998;273:25804–25808.
26.
Vasquez-Vivar J, Kalyanaraman B, Martasek P, Hogg N,
Masters BS, Karoui H, Tordo P, Pritchard KA Jr. Superoxide generation
by endothelial nitric oxide synthase: the influence of
cofactors. Proc Natl Acad Sci U S A. 1998;95:9220–9225.
27. Cordellini S, Nigro D, Carvalho MH, Fortes ZB, Scivoletto R. Reactivity of macro- and microvessels of DOCA-salt hypertensive rats: role of the endothelial cell. Braz J Med Biol Res. 1988;21:845–849.[Medline] [Order article via Infotrieve]
28. Huie RE, Padmaja S. The reaction of NO with superoxide. Free Radic Res Commun. 1993;18:195–199.[Medline] [Order article via Infotrieve]
29.
Schnackenberg CG, Welch WJ, Wilcox CS. Normalization of
blood pressure and renal vascular resistance in SHR with a
membrane-permeable superoxide dismutase mimetic: role of nitric oxide.
Hypertension. 1998;32:59–64.
30.
Schnackenberg CG, Wilcox CS. Two-week administration of
tempol attenuates both hypertension and renal excretion of 8-Iso
prostaglandin F2
.
Hypertension. 1999;33:424–428.
31.
Huang M, Hester RL, Guyton AC, Norman RA Jr.
Hemodynamic studies in DOCA-salt hypertensive rats
after opening of an arteriovenous fistula. Am J
Physiol. 1992;262:H1802–H1808.
32.
Huang M, Hester RL, Coleman TG, Smith MJ, Guyton AC.
Development of hypertension in animals with reduced total
peripheral resistance. Hypertension. 1992;20:828–833.
33.
Potter DD, Sobey CG, Tompkins PK, Rossen JD, Heistad
DD. Evidence that macrophages in atherosclerotic lesions
contain angiotensin II. Circulation. 1998;98:800–807.
34. Harrison D, Schiavi P, Falgui B. Renovascular hypertension, aortic superoxide production: effect of perindopril and indapamide. Am J Hypertens. 1999;12:50A. Abstract.
35. Cosentino F, Patton S, d’Uscio LV, Werner ER, Werner-Felmayer G, Moreau P, Malinski T, Luscher TF. Tetrahydrobiopterin alters superoxide and nitric oxide release in prehypertensive rats. J Clin Invest. 1998;101:1530–1537.[Medline] [Order article via Infotrieve]
36.
Khan BV, Harrison DG, Olbrych MT, Alexander RW, Medford
RM. Nitric oxide regulates vascular cell adhesion molecule 1 gene
expression and redox-sensitive transcriptional events in human vascular
endothelial cells. Proc Natl Acad Sci
U S A. 1996;93:9114–9119.
37.
Zeiher AM, Fisslthaler B, Schray-Utz B, Busse R. Nitric
oxide modulates the expression of monocyte chemoattractant protein 1 in
cultured human endothelial cells. Circ Res. 1995;76:980–986.
38.
Wee Soo S, Hong YH, Peng HB, De Caterina R, Libby P,
Liao JK. Nitric oxide attenuates vascular smooth muscle cell activation
by interferon-gamma: the role of constitutive NF-kappaB activity.
J Biol Chem. 1996;271:11317–11324.
This article has been cited by other articles:
 |
|
 |
|
  L. A. Lesniewski, M. L. Connell, J. R. Durrant, B. J. Folian, M. C. Anderson, A. J. Donato, and D. R. Seals B6D2F1 Mice Are a Suitable Model of Oxidative Stress-Mediated Impaired Endothelium-Dependent Dilation With Aging J Gerontol A Biol Sci Med Sci, February 10, 2009; (2009) gln049v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Li, X. Dai, S. Watts, D. Kreulen, and G. Fink Increased superoxide levels in ganglia and sympathoexcitation are involved in sarafotoxin 6c-induced hypertension Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2008; 295(5): R1546 - R1554. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. C. Viel, K. Benkirane, D. Javeshghani, R. M. Touyz, and E. L. Schiffrin Xanthine oxidase and mitochondria contribute to vascular superoxide anion generation in DOCA-salt hypertensive rats Am J Physiol Heart Circ Physiol, July 1, 2008; 295(1): H281 - H288. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. M. Paravicini and R. M. Touyz NADPH Oxidases, Reactive Oxygen Species, and Hypertension: Clinical implications and therapeutic possibilities Diabetes Care, February 1, 2008; 31(Supplement_2): S170 - S180. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Macarthur, T. C. Westfall, and G. H. Wilken Oxidative stress attenuates NO-induced modulation of sympathetic neurotransmission in the mesenteric arterial bed of spontaneously hypertensive rats Am J Physiol Heart Circ Physiol, January 1, 2008; 294(1): H183 - H189. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. A. Korshunov, M. Daul, M. P. Massett, and B. C. Berk Axl Mediates Vascular Remodeling Induced by Deoxycorticosterone Acetate Salt Hypertension Hypertension, December 1, 2007; 50(6): 1057 - 1062. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. J. Guzik, N. E. Hoch, K. A. Brown, L. A. McCann, A. Rahman, S. Dikalov, J. Goronzy, C. Weyand, and D. G. Harrison Role of the T cell in the genesis of angiotensin II induced hypertension and vascular dysfunction J. Exp. Med., October 1, 2007; 204(10): 2449 - 2460. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Cao, X. Dai, L. M. Parker, and D. L. Kreulen Differential Regulation of NADPH Oxidase in Sympathetic and Sensory Ganglia in Deoxycorticosterone Acetate Salt Hypertension Hypertension, October 1, 2007; 50(4): 663 - 671. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Wu, W. C. Willett, N. Rifai, and E. B. Rimm Plasma Fluorescent Oxidation Products as Potential Markers of Oxidative Stress for Epidemiologic Studies Am. J. Epidemiol., September 1, 2007; 166(5): 552 - 560. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Xu, G. D. Fink, and J. J. Galligan Increased sympathetic venoconstriction and reactivity to norepinephrine in mesenteric veins in anesthetized DOCA-salt hypertensive rats Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H160 - H168. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. D. Widder, T. J. Guzik, C. F.H. Mueller, R. E. Clempus, H. H.H.W. Schmidt, S. I. Dikalov, K. K. Griendling, D. P. Jones, and D. G. Harrison Role of the Multidrug Resistance Protein-1 in Hypertension and Vascular Dysfunction Caused by Angiotensin II Arterioscler Thromb Vasc Biol, April 1, 2007; 27(4): 762 - 768. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. A. Ko, F. Amiri, N. R. Pandey, D. Javeshghani, E. Leibovitz, R. M. Touyz, and E. L. Schiffrin Resistance artery remodeling in deoxycorticosterone acetate-salt hypertension is dependent on vascular inflammation: evidence from m-CSF-deficient mice Am J Physiol Heart Circ Physiol, April 1, 2007; 292(4): H1789 - H1795. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K.-T. Kang, J. C. Sullivan, J. M. Sasser, J. D. Imig, and J. S. Pollock Novel Nitric Oxide Synthase-Dependent Mechanism of Vasorelaxation in Small Arteries From Hypertensive Rats Hypertension, April 1, 2007; 49(4): 893 - 901. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-W. Gu, N. Tian, M. Shparago, W. Tan, A. P. Bailey, and R. D. Manning Jr. Renal NF-{kappa}B activation and TNF-{alpha} upregulation correlate with salt-sensitive hypertension in Dahl salt-sensitive rats Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2006; 291(6): R1817 - R1824. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Xu, W. F. Jackson, G. D. Fink, and J. J. Galligan Activation of Potassium Channels by Tempol in Arterial Smooth Muscle Cells From Normotensive and Deoxycorticosterone Acetate-Salt Hypertensive Rats Hypertension, December 1, 2006; 48(6): 1080 - 1087. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. M. Paravicini and R. M. Touyz Redox signaling in hypertension Cardiovasc Res, July 15, 2006; 71(2): 247 - 258. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Jin, Z. Ying, R. H. P. Hilgers, J. Yin, X. Zhao, J. D. Imig, and R. C. Webb Increased RhoA/Rho-Kinase Signaling Mediates Spontaneous Tone in Aorta from Angiotensin II-Induced Hypertensive Rats J. Pharmacol. Exp. Ther., July 1, 2006; 318(1): 288 - 295. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Sapna, S. K. Ranjith, and K. Shivakumar Cardiac fibrogenesis in magnesium deficiency: a role for circulating angiotensin II and aldosterone Am J Physiol Heart Circ Physiol, July 1, 2006; 291(1): H436 - H440. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Dai, X. Cao, and D. L. Kreulen Superoxide anion is elevated in sympathetic neurons in DOCA-salt hypertension via activation of NADPH oxidase Am J Physiol Heart Circ Physiol, March 1, 2006; 290(3): H1019 - H1026. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Vidal, Y. Sun, S. K. Bhattacharya, R. A. Ahokas, I. C. Gerling, and K. T. Weber Calcium paradox of aldosteronism and the role of the parathyroid glands Am J Physiol Heart Circ Physiol, January 1, 2006; 290(1): H286 - H294. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. E. Lau, J. J. Galligan, D. L. Kreulen, and G. D. Fink Activation of ETB receptors increases superoxide levels in sympathetic ganglia in vivo Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2006; 290(1): R90 - R95. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Xu, X. Bian, S. W. Watts, and A. Hlavacova Activation of Vascular BK Channel by Tempol in DOCA-Salt Hypertensive Rats Hypertension, November 1, 2005; 46(5): 1154 - 1162. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. S. Wilcox Oxidative stress and nitric oxide deficiency in the kidney: a critical link to hypertension? Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2005; 289(4): R913 - R935. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. J. Duffy, E. S. Biegelsen, R. T. Eberhardt, D. F. Kahn, B. A. Kingwell, and J. A. Vita Low-Renin Hypertension With Relative Aldosterone Excess Is Associated With Impaired NO-Mediated Vasodilation Hypertension, October 1, 2005; 46(4): 707 - 713. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. F.H. Mueller, J. D. Widder, J. S. McNally, L. McCann, D. P. Jones, and D. G. Harrison The Role of the Multidrug Resistance Protein-1 in Modulation of Endothelial Cell Oxidative Stress Circ. Res., September 30, 2005; 97(7): 637 - 644. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-F. Xia, G. Bledsoe, L. Chao, and J. Chao Kallikrein gene transfer reduces renal fibrosis, hypertrophy, and proliferation in DOCA-salt hypertensive rats Am J Physiol Renal Physiol, September 1, 2005; 289(3): F622 - F631. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Thakali, S. L. Demel, G. D. Fink, and S. W. Watts Endothelin-1-induced contraction in veins is independent of hydrogen peroxide Am J Physiol Heart Circ Physiol, September 1, 2005; 289(3): H1115 - H1122. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Fujita, T. Kuwaki, K. Ando, and T. Fujita Sympatho-Inhibitory Action of Endogenous Adrenomedullin Through Inhibition of Oxidative Stress in the Brain Hypertension, June 1, 2005; 45(6): 1165 - 1172. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. K. Griendling ATVB In Focus: Redox Mechanisms in Blood Vessels Arterioscler Thromb Vasc Biol, February 1, 2005; 25(2): 272 - 273. [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]
|
|
|
|
|
|
J. M. Williams, J. S. Pollock, and D. M. Pollock Arterial Pressure Response to the Antioxidant Tempol and ETB Receptor Blockade in Rats on a High-Salt Diet Hypertension, November 1, 2004; 44(5): 770 - 775. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Jin, Z. Ying, and R. C. Webb Activation of Rho/Rho kinase signaling pathway by reactive oxygen species in rat aorta Am J Physiol Heart Circ Physiol, October 1, 2004; 287(4): H1495 - H1500. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. M. Campese, S. Ye, H. Zhong, V. Yanamadala, Z. Ye, and J. Chiu Reactive oxygen species stimulate central and peripheral sympathetic nervous system activity Am J Physiol Heart Circ Physiol, August 1, 2004; 287(2): H695 - H703. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Ungvari, A. Csiszar, P. M. Kaminski, M. S. Wolin, and A. Koller Chronic High Pressure-Induced Arterial Oxidative Stress: Involvement of Protein Kinase C-Dependent NAD(P)H Oxidase and Local Renin-Angiotensin System Am. J. Pathol., July 1, 2004; 165(1): 219 - 226. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Sasser, J. C. Sullivan, A. A. Elmarakby, B. E. Kemp, D. M. Pollock, and J. S. Pollock Reduced NOS3 Phosphorylation Mediates Reduced NO/cGMP Signaling in Mesenteric Arteries of Deoxycorticosterone Acetate-Salt Hypertensive Rats Hypertension, May 1, 2004; 43(5): 1080 - 1085. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Dai, J. J. Galligan, S. W. Watts, G. D. Fink, and D. L. Kreulen Increased O2{middle dot}- Production and Upregulation of ETB Receptors by Sympathetic Neurons in DOCA-Salt Hypertensive Rats Hypertension, May 1, 2004; 43(5): 1048 - 1054. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. T. Weber From Inflammation to Fibrosis: A Stiff Stretch of Highway Hypertension, April 1, 2004; 43(4): 716 - 719. [Full Text] [PDF]
|
|
|
|
 |
|
 F. K Shieh, E. Kotlyar, and F. Sam Aldosterone and cardiovascular remodelling: focus on myocardial failure Journal of Renin-Angiotensin-Aldosterone System, March 1, 2004; 5(1): 3 - 13. [Abstract] [PDF]
|
|
|
|
|
|
H. Xu, G. D. Fink, and J. J. Galligan Tempol Lowers Blood Pressure and Sympathetic Nerve Activity But Not Vascular O2- in DOCA-Salt Rats Hypertension, February 1, 2004; 43(2): 329 - 334. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 M. Hermann, G. Camici, A. Fratton, D. Hurlimann, F. C. Tanner, J. P. Hellermann, M. Fiedler, J. Thiery, M. Neidhart, R. E. Gay, et al. Differential Effects of Selective Cyclooxygenase-2 Inhibitors on Endothelial Function in Salt-Induced Hypertension Circulation, November 11, 2003; 108(19): 2308 - 2311. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. K. Griendling and G. A. FitzGerald Oxidative Stress and Cardiovascular Injury: Part II: Animal and Human Studies Circulation, October 28, 2003; 108(17): 2034 - 2040. [Full Text] [PDF]
|
|
|
|
|
|
B. Pitt Aldosterone Blockade in Patients With Systolic Left Ventricular Dysfunction Circulation, October 14, 2003; 108(15): 1790 - 1794. [Full Text] [PDF]
|
|
|
|
|
|
G. E. Callera, R. M. Touyz, S. A. Teixeira, M. N. Muscara, M. H. C. Carvalho, Z. B. Fortes, D. Nigro, E. L. Schiffrin, and R. C. Tostes ETA Receptor Blockade Decreases Vascular Superoxide Generation in DOCA-Salt Hypertension Hypertension, October 1, 2003; 42(4): 811 - 817. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Ungvari, A. Csiszar, A. Huang, P. M. Kaminski, M. S. Wolin, and A. Koller High Pressure Induces Superoxide Production in Isolated Arteries Via Protein Kinase C-Dependent Activation of NAD(P)H Oxidase Circulation, September 9, 2003; 108(10): 1253 - 1258. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-S. Zheng, X.-Q. Yang, K. J. Lookingland, G. D. Fink, C. Hesslinger, G. Kapatos, I. Kovesdi, and A. F. Chen Gene Transfer of Human Guanosine 5'-Triphosphate Cyclohydrolase I Restores Vascular Tetrahydrobiopterin Level and Endothelial Function in Low Renin Hypertension Circulation, September 9, 2003; 108(10): 1238 - 1245. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Li, S. W. Watts, A. K. Banes, J. J. Galligan, G. D. Fink, and A. F. Chen NADPH Oxidase-Derived Superoxide Augments Endothelin-1-Induced Venoconstriction in Mineralocorticoid Hypertension Hypertension, September 1, 2003; 42(3): 316 - 321. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Lassegue and R. E. Clempus Vascular NAD(P)H oxidases: specific features, expression, and regulation Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2003; 285(2): R277 - R297. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. F. Reckelhoff and J. C. Romero Role of oxidative stress in angiotensin-induced hypertension Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2003; 284(4): R893 - R912. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. F. Keaney Jr, M. G. Larson, R. S. Vasan, P. W.F. Wilson, I. Lipinska, D. Corey, J. M. Massaro, P. Sutherland, J. A. Vita, and E. J. Benjamin Obesity and Systemic Oxidative Stress: Clinical Correlates of Oxidative Stress in The Framingham Study Arterioscler Thromb Vasc Biol, March 1, 2003; 23(3): 434 - 439. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Li, J. J. Galligan, G. D. Fink, and A. F. Chen Vasopressin Induces Vascular Superoxide Via Endothelin-1 in Mineralocorticoid Hypertension Hypertension, March 1, 2003; 41(3): 663 - 668. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. M. Hoagland, K. G. Maier, and R. J. Roman Contributions of 20-HETE to the Antihypertensive Effects of Tempol in Dahl Salt-Sensitive Rats Hypertension, March 1, 2003; 41(3): 697 - 702. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Li, G. D. Fink, S. W. Watts, C. A. Northcott, J. J. Galligan, P. J. Pagano, and A. F. Chen Endothelin-1 Increases Vascular Superoxide via EndothelinA-NADPH Oxidase Pathway in Low-Renin Hypertension Circulation, February 25, 2003; 107(7): 1053 - 1058. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Kobori, A. Nishiyama, L. M. Harrison-Bernard, and L. G. Navar Urinary Angiotensinogen as an Indicator of Intrarenal Angiotensin Status in Hypertension Hypertension, January 1, 2003; 41(1): 42 - 49. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. L. Sutliff, S. Dikalov, D. Weiss, J. Parker, S. Raidel, A. K. Racine, R. Russ, C. P. Haase, W. R. Taylor, and W. Lewis Nucleoside reverse transcriptase inhibitors impair endothelium-dependent relaxation by increasing superoxide Am J Physiol Heart Circ Physiol, December 1, 2002; 283(6): H2363 - H2370. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Sun, J. Zhang, L. Lu, S. S. Chen, M. T. Quinn, and K. T. Weber Aldosterone-Induced Inflammation in the Rat Heart : Role of Oxidative Stress Am. J. Pathol., November 1, 2002; 161(5): 1773 - 1781. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Landmesser, H. Cai, S. Dikalov, L. McCann, J. Hwang, H. Jo, S. M. Holland, and D. G. Harrison Role of p47phox in Vascular Oxidative Stress and Hypertension Caused by Angiotensin II Hypertension, October 1, 2002; 40(4): 511 - 515. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Xu, G. D. Fink, and J. J. Galligan Nitric oxide-independent effects of tempol on sympathetic nerve activity and blood pressure in DOCA-salt rats Am J Physiol Heart Circ Physiol, September 1, 2002; 283(3): H885 - H892. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Rathaus and J. Bernheim Oxygen species in the microvascular environment: regulation of vascular tone and the development of hypertension Nephrol. Dial. Transplant., February 1, 2002; 17(2): 216 - 221. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Li, E. Crockett, D. H. Wang, J. J. Galligan, G. D. Fink, and A. F. Chen Gene Transfer of Endothelial NO Synthase and Manganese Superoxide Dismutase on Arterial Vascular Cell Adhesion Molecule-1 Expression and Superoxide Production in Deoxycorticosterone Acetate-Salt Hypertension Arterioscler Thromb Vasc Biol, February 1, 2002; 22(2): 249 - 255. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C. Sullivan, D. M. Pollock, and J. S. Pollock Altered Nitric Oxide Synthase 3 Distribution in Mesenteric Arteries of Hypertensive Rats Hypertension, February 1, 2002; 39(2): 597 - 602. [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]
|
|
|
|
|
|
T. Aizawa, N. Ishizaka, S.-I. Usui, N. Ohashi, M. Ohno, and R. Nagai Angiotensin II and Catecholamines Increase Plasma Levels of 8-Epi-Prostaglandin F2{alpha} With Different Pressor Dependencies in Rats Hypertension, January 1, 2002; 39(1): 149 - 154. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Zalba, G. S. Jose, M. U. Moreno, M. A. Fortuno, A. Fortuno, F. J. Beaumont, and J. Diez Oxidative Stress in Arterial Hypertension: Role of NAD(P)H Oxidase Hypertension, December 1, 2001; 38(6): 1395 - 1399. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Beswick, A. M. Dorrance, R. Leite, and R. C. Webb NADH/NADPH Oxidase and Enhanced Superoxide Production in the Mineralocorticoid Hypertensive Rat Hypertension, November 1, 2001; 38(5): 1107 - 1111. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. P. Didion, C. A. Hathaway, and F. M. Faraci Superoxide levels and function of cerebral blood vessels after inhibition of CuZn-SOD Am J Physiol Heart Circ Physiol, October 1, 2001; 281(4): H1697 - H1703. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Okuda, N. Inoue, H. Azumi, T. Seno, Y. Sumi, K.-i. Hirata, S. Kawashima, Y. Hayashi, H. Itoh, J. Yodoi, et al. Expression of Glutaredoxin in Human Coronary Arteries: Its Potential Role in Antioxidant Protection Against Atherosclerosis Arterioscler Thromb Vasc Biol, September 1, 2001; 21(9): 1483 - 1487. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Chen, R. M. Touyz, J. B. Park, and E. L. Schiffrin Antioxidant Effects of Vitamins C and E Are Associated With Altered Activation of Vascular NADPH Oxidase and Superoxide Dismutase in Stroke-Prone SHR Hypertension, September 1, 2001; 38(3): 606 - 611. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Katoh, Y. Kurosawa, K. Tanaka, A. Watanabe, H. Doi, and H. Narita Fluvastatin inhibits O2- and ICAM-1 levels in a rat model with aortic remodeling induced by pressure overload Am J Physiol Heart Circ Physiol, August 1, 2001; 281(2): H655 - H660. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Patterson, N. R. Madamanchi, and M. S. Runge The Oxidative Paradox : Another Piece in the Puzzle Circ. Res., December 8, 2000; 87(12): 1074 - 1076. [Full Text] [PDF]
|
|
|
|
|
|
K. K. Griendling, D. Sorescu, B. Lassegue, and M. Ushio-Fukai Modulation of Protein Kinase Activity and Gene Expression by Reactive Oxygen Species and Their Role in Vascular Physiology and Pathophysiology Arterioscler Thromb Vasc Biol, October 1, 2000; 20(10): 2175 - 2183. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. P. Didion and F. M. Faraci Effects of NADH and NADPH on superoxide levels and cerebral vascular tone Am J Physiol Heart Circ Physiol, February 1, 2002; 282(2): H688 - H695. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Duchesne, J. D. Klein, J. B. Velotta, J. J. Doran, P. Rouillard, B. R. Roberts, A. A. McDonough, and J. M. Sands UT-A Urea Transporter Protein in Heart: Increased Abundance During Uremia, Hypertension, and Heart Failure Circ. Res., July 20, 2001; 89(2): 139 - 145. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||