Published online before print April 29, 2002, doi: 10.1161/01.CIR.0000016049.86468.23
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 2002;105:2296.)
© 2002 American Heart Association, Inc.
Basic Science Reports |
Structure, Endothelial Function, Cell Growth, and Inflammation in Blood Vessels of Angiotensin II–Infused Rats
Role of Peroxisome Proliferator–Activated Receptor-
From the Canadian Institutes of Health Research Multidisciplinary Research Group on Hypertension (Q.N.D., M.E.M., A.V., M.F.N., F.A., E.L.S.), Hyperlipidemia and Atherosclerosis Research Group (J.S.C.), Clinical Research Institute of Montreal, Montreal, Quebec, Canada; and Regensburg University Clinic (D.E.), Regensburg, Germany.
Correspondence to Ernesto L. Schiffrin, MD, PhD, FRCPC, Clinical Research Institute of Montreal, 110 Pine Ave W, Montreal, Quebec, Canada H2W 1R7. E-mail schiffe{at}ircm.qc.ca
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
Background— Pioglitazone and rosiglitazone, thiazolidinedione peroxisome proliferator–activated receptor-
(PPAR) activators, reduce blood pressure (BP) in some hypertensive models by unclear mechanisms. We tested the hypothesis that pioglitazone or rosiglitazone would prevent BP elevation and vascular dysfunction in angiotensin (Ang) II–infused rats by direct vascular effects.
Methods and Results— Sprague-Dawley rats received Ang II (120 ng · kg-1 · min-1 SC) with or without pioglitazone (10 mg · kg-1 · d-1) or rosiglitazone (5 mg · kg-1 · d-1) for 7 days. Systolic BP, elevated in Ang II–infused rats (176±5 mm Hg) versus controls (109±2 mm Hg, P<0.01), was reduced by pioglitazone (134±2 mm Hg) or rosiglitazone (123±2 mm Hg). In mesenteric small arteries studied in a pressurized myograph, media/lumen ratio was increased (P<0.05) and acetylcholine-induced relaxation impaired in Ang II–infused rats (P<0.05); both were normalized by the thiazolidinediones. In Ang II–infused rats, vascular DNA synthesis (by 3H-thymidine incorporation); expression of cell cycle proteins cyclin D1 and cdk4, angiotensin II type 1 receptors, vascular cell adhesion molecule-1, and platelet and endothelial cell adhesion molecule; and nuclear factor-
B activity were increased. These changes were abrogated by pioglitazone or rosiglitazone.
Conclusions— Thiazolidinedione PPAR- activators attenuated the development of hypertension, corrected structural abnormalities, normalized cell growth, and improved endothelial dysfunction induced by Ang II and prevented upregulation of angiotensin II type 1 receptors, cell cycle proteins, and proinflammatory mediators. Thiazolidinediones may be useful in the prevention and/or treatment of hypertension, particularly when it is associated with insulin resistance or diabetes mellitus.
Key Words: hypertension • arteries • remodeling • muscle, smooth • inflammation
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Insulin resistance has emerged as a mechanism linking diabetes mellitus and hypertension.1 Thiazolidinediones (TZDs) such as pioglitazone and rosiglitazone are high-affinity ligands for peroxisome proliferator–activated receptor (PPAR)-
, a transcription factor of the nuclear hormone receptor superfamily,2 and are used as insulin-sensitizing drugs in type II diabetes mellitus. TZDs increase transcription of certain insulin-sensitive genes by binding to nuclear PPAR-, which together with the retinoid X receptor binds to specific DNA sequences, the peroxisome proliferator response elements.3 Expression of PPAR-, initially thought to be restricted to adipose tissue, is now known to occur in endothelium,4 vascular smooth muscle cells (VSMCs),5 and monocytes/macrophages.6 Angiotensin (Ang) II plays a major role in hypertension. Ang II–induced hypertensive rats exhibit abnormal vascular structure.7 VSMC growth, apoptosis, cell migration, inflammation, and increased deposition of extracellular matrix proteins such as collagen and fibronectin, as well as changes in anchoring of cells to the fibrillar components of the extracellular matrix, are some of the processes that contribute to vascular remodeling induced by Ang II.8
TZDs have blood pressure (BP)–lowering effects,9,10 but mechanisms for this are unclear. PPAR- agonists may directly modulate vascular structure and function independently of their role on lipid metabolism. Here, we tested the hypothesis that PPAR- activators such as pioglitazone or rosiglitazone have effects on Ang II type 1 (AT1) receptors and that Ang II–induced increases in DNA synthesis, cell cycle proteins, nuclear factor-B (NF-B), vascular cell adhesion molecule-1 (VCAM-1), and platelet and endothelial cell adhesion molecule (PECAM) are abrogated by these agents in Ang II–infused rats.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Animal Experiments
The study was approved by the Animal Care Committee of the Clinical Research Institute of Montreal and followed guidelines of the Canadian Council for Animal Care. Male Sprague-Dawley rats (weight 200 g; Corporation Charles River Canada, Saint-Constant, Quebec, Canada) were infused subcutaneously by use of Alzet osmotic minipumps (Alza Corp) with Ile5-Ang II (Peninsula) at a dose of 120 ng · kg-1 · min-1 for 7 days. Pioglitazone (10 mg · kg-1 · d-1) and rosiglitazone (5 mg · kg-1 · d-1) were offered mixed with food. Ang II–infused rats were also treated with hydralazine (25 mg · kg-1 · d-1) in drinking water to evaluate effects of BP lowering. Systolic BP was measured by the tail-cuff method. Rats were not fasted overnight, and they were killed by decapitation. The mesenteric bed was dissected; one segment was used for preparation of small arteries, and the rest was cleaned of fat, frozen in liquid nitrogen, and kept at -80°C for Western blot assay and for DNA extraction. A portion of aorta was fixed in 10% buffered formalin solution and embedded in paraffin. Tissue sections (7 µm thick) were prepared for immunohistochemical analysis. Fat and endothelium were removed from another portion of aorta that was then frozen in liquid nitrogen and kept at -80°C for measurement of NF-
B activity.
Preparation and Study of Small Arteries
Third-order superior mesenteric arteries (length 
2 mm) were placed in cold physiological salt solution containing (in mmol/L) NaCl 120, NaHCO3 25, KCl 4.7, KH2PO4 1.2, MgSO4 1.2, CaCl2 2.5, EDTA 0.026, and glucose 5.5. They were mounted on glass microcannulas in a pressurized myograph.11 Endothelium-dependent relaxation was assessed with cumulative doses of acetylcholine (10-9 to 10-4 mol/L) after precontraction with 10-5 mol/L norepinephrine. Endothelium-independent relaxation was assessed with cumulative doses of sodium nitroprusside (SNP; 10-8 to 10-3 mol/L). Vessels were then deactivated by perfusion with Ca2+-free physiological salt solution containing 10 mmol/L EGTA for 30 minutes. Lumen and media were measured with intraluminal pressure at 45 mm Hg.
Evaluation of Collagen Deposition in Aorta
Paraffin-embedded sections of aorta were stained with Sirius Red. Collagen in the media was quantified microscopically with the Northern Eclipse imaging program.
Evaluation of DNA Synthesis
DNA synthesis in mesenteric arteries was evaluated by radiolabeled 3H-thymidine incorporation.12 Rats received intraperitoneal injections of [methyl-3H] thymidine (0.5 mCi/kg, ICN Biomedicals Inc) 24 hours before they were killed. DNA was extracted with phenol/chloroform and its concentration determined spectrophotometrically. DNA specific activity (cpm/100 µg of DNA) reflecting the incorporation of 3H-thymidine into smooth muscle DNA over the last 24 hours in vivo was measured by scintillation counting.
Western Blot Analysis of Cyclin D1, cdk4, VCAM-1, PECAM, PPAR-, and AT1 and AT2 Receptors
Protein was extracted from frozen tissue,12 and concentration was determined with the Micro BCA protein assay kit (Pierce). Aliquots were separated by electrophoresis on a 10% to 15% polyacrylamide gel at 100 V for 1 hour and transferred onto a polyvinylidene difluoride membrane in a cooling system at 100 V for 1 hour. Membranes were incubated with specific antibody to cyclin D1, cdk4, VCAM-1, PECAM, PPAR-, and AT1 and AT2 receptors (Santa Cruz Biotechnology Inc). Signals were revealed with chemiluminescence and visualized autoradiographically. Optical density of bands was quantified by scanning and with ImageQuant (Molecular Dynamics). The density of the bands from each blot was normalized to that of controls (taken as 100%). Mean±SEM values were calculated from 4 blots.
Electrophoretic Mobility Shift Assay for NF-B
Frozen aorta was homogenized; suspended in solution containing 50 mmol/L Tris (pH 7.4), 1 mmol/L sodium orthovanadate, 1 µg/mL pepstatin, 1 µg/mL aprotinin, and 1 µg/mL leupeptin; and centrifuged (4000g, 4 minutes, 4°C).13 The resuspended pellet was lysed for 30 minutes in 20 mmol/L HEPES, pH 7.9, containing 350 mmol/L NaCl, 20% glycerol, 1 mmol/L MgCl2, 0.5 mmol/L EDTA, 0.1 mmol/L EGTA, 1% NP-40, 1 mmol/L PMSF, 1 mmol/L sodium orthovanadate, 1 µg/mL pepstatin, 1 µg/mL aprotinin, and 1 µg/mL leupeptin and centrifuged (13 000g, 10 minutes, 4°C). The supernatant was stored at -80°C. Protein concentration was quantified by BioRad reagent. Twenty micrograms of nuclear protein was incubated at room temperature for 30 minutes in binding reaction medium (50 mmol/L Tris-HCl, 250 mmol/L NaCl, 20% glycerol, 2.5 mmol/L EDTA, 2.5 mmol/L DTT, 5 mmol/L MgCl2, and 0.25 mg/mL poly dI-dC) with 0.5 ng of 32P-dATP end-labeled double-stranded oligonucleotide containing the NF-B binding site (Promega, 5'-AGTTGAGGGGACTTTCCCAGGC-3', based on the rat sequence) from the major histocompatibility complex enhancer. HeLa cell nuclear extracts and water were respectively positive and negative controls. NF-B (p65-x) antibody from Santa Cruz was used for supershift. In competition assays, 50 ng of unlabeled oligonucleotides was used. The DNA-protein complexes were analyzed on 4% polyacrylamide gel in 0.5X Tris-borate-EDTA buffer. The gel was then dried and exposed to 32P-sensitive screen. Optical density in the region of NF-B (p65) was quantified for each lane with the PhosphoImager system. Mean±SEM values were calculated from 3 electrophoretic mobility shift assays.
Measurement of Plasma Renin Activity, Aldosterone, and Lipids
Plasma renin activity was measured by radioimmunoassay of Ang I produced after a 2-hour incubation of plasma at 37°C and pH 6.5.14 Plasma aldosterone was measured with the ALDOCTK-2 (P2714) assay kit from DiaSorin. Plasma was assayed for total (free and esterified) cholesterol and triacylglycerol with a COBAS MIRA-S automated analyzer with enzymatic reagents (Hoffman-LaRoche). Nonesterified fatty acids were measured by enzymatic colorimetric method (Wako NEFA C test kit).
Data Analysis
Values are presented as mean±SEM. Results were compared by 1-way ANOVA, followed by Tukey-Kramer test. P<0.05 was considered significant.
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Body Weight, BP, Plasma Renin Activity, Aldosterone, and Lipids
After 7-day treatment, body weight was similar in all groups (Table 1). The BP increase induced by Ang II infusion (P<0.01 versus control) was abolished by pioglitazone and rosiglitazone (Table 1) and, in parallel experiments, by hydralazine (124±1 mm Hg; Figure 1A). Rosiglitazone slightly increased BP in normal rats.
|
|
P<0.05 vs Ang II group. B, Media/lumen ratio (as %) in small mesenteric arteries of Ang II–infused rats treated without or with hydralazine for 7 days. Results are mean±SEM (n=5 to 8 per group). *P<0.05 vs control. C, Endothelium-dependent relaxation in response to acetylcholine (ACH) in small mesenteric arteries of Ang II–infused rats treated without or with hydralazine for 7 days. Results are mean±SEM (n=5 to 8 per group). Relaxation is expressed as percent increase in intraluminal diameter after precontraction with 10-5 mol/L norepinephrine. *P<0.05 vs control. D, Electrophoretic mobility shift assay of NF-As expected, plasma renin activity was significantly depressed in Ang II–infused rats and was unaffected by pioglitazone or rosiglitazone (Table 1). The plasma aldosterone/renin activity ratio rose 100-fold with Ang II and was unaffected by pioglitazone or rosiglitazone. Ang II, pioglitazone, and rosiglitazone had no effect on plasma cholesterol, triacylglycerol, or nonesterified fatty acids.
Collagen Deposition in Aorta
Ang II, pioglitazone, and rosiglitazone did not affect vascular collagen deposition after the 7-day Ang II infusion (Table 2).
|
Morphology and Endothelial Function of Resistance Arteries
Ang II infusion resulted in an increase (P<0.05) in media/lumen ratio of resistance arteries (Table 2), which was normalized by treatment with pioglitazone or rosiglitazone (Table 2). Hydralazine did not affect vascular structural changes induced by Ang II (Figure 1B). Media cross-sectional area of resistance arteries was similar in all groups.
Ang II–infused rats exhibited impaired acetylcholine-induced relaxation (Figures 1C and 2A), which improved (P<0.05) under pioglitazone and rosiglitazone (Figure 2A) but not hydralazine (Figure 1C). Endothelium-independent relaxation by SNP was similar in all groups (Figure 1B). Relaxation to acetylcholine and SNP was unaffected by the TZDs alone (data not shown).
|
Resistance Artery DNA Synthesis and Expression of Cell Cycle Proteins
Vascular DNA synthesis (3H-thymidine incorporation) increased 1.8-fold in Ang II–infused rats (Figure 3A) and decreased with pioglitazone and rosiglitazone. Expression of cyclin D1 and cdk4 increased 3- and 4-fold, respectively, in Ang II–infused rats (Figure 3B). This effect was abrogated by the TZDs (Figure 3B).
|
Vascular Expression of Angiotensin Receptors
Expression of AT1 and AT2 receptors in resistance arteries of Ang II–infused rats increased 2-fold (Figure 4). Pioglitazone- and rosiglitazone-treated Ang II–infused rats had normal levels of AT1 receptors. Expression of AT2 receptors increased 2-fold in rats treated with the TZDs, whether Ang II–infused or not.
|
Vascular Expression of NF-B and Adhesion Molecules
NF-B, which regulates expression of inflammatory mediators, was activated 3-fold in blood vessels of Ang II–infused rats (Figures 5A and 1D), and VCAM-1 and PECAM expression increased significantly (Figures 5B and 5C and Figure 1E). These effects were abolished by pioglitazone and rosiglitazone (Figures 5B and 5C) but not by hydralazine (Figures 1D and 1E). The TZDs alone had no effect on NF-B, VCAM-1, or PECAM.
|
Vascular Expression of PPAR-
PPAR- expression in mesenteric arteries was unaffected by Ang II but was enhanced by pioglitazone or rosiglitazone (Figure 6).
|
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
In this study, pioglitazone and rosiglitazone prevented hypertension in Ang II–infused rats and abrogated the structural, functional, and molecular changes in blood vessels. We show the novel finding that the PPAR-
activators had direct effects on the vascular wall, with downregulation of AT1 receptors and upregulation of AT2 receptors that led to inhibition of cell growth and inflammation.
TZDs have antihypertensive effects in other hypertensive models.9,10 The novel finding that these agents reduced resistance artery remodeling may be explained by a direct action of TZDs on the vessel wall. BP lowering does not appear to play a role, because hydralazine decreased BP without any effect on vascular structure, endothelial function, or inflammatory mediators. These in vivo data confirm and extend results from in vitro studies in which PPAR- ligands were shown to downregulate AT1 receptor expression15–17 and inhibit Ang II–stimulated DNA synthesis in VSMCs18 by modulation of cyclin-dependent kinase inhibitors.19 Pioglitazone and rosiglitazone also decreased cell growth in small arteries. We recently found that rosiglitazone induced VSMC apoptosis, which could contribute to this effect (unpublished data). Although molecular mechanisms remain to be clarified, inhibition of growth and acceleration of apoptotic rate by PPAR- via increased expression of AT2 receptors may decrease the cell proliferation induced by Ang II via AT1 receptors. Ang II also induces vascular remodeling via collagen deposition.8,20 The absence of changes in collagen found during the short 7-day Ang II infusion in the present study may contribute to the absence of net vascular growth observed in the Ang II–infused groups. Indeed, small artery structural changes after Ang II infusion were the so-called eutrophic remodeling (unchanged media cross-sectional area).21 A role of AT1 receptors in the Ang II effects reported here is supported by previous data that demonstrated that ACE inhibition or antagonism of AT1 receptors prevented or reversed hypertensive changes in resistance artery structure.22
Rosiglitazone used alone slightly increased BP. TZDs may have direct vascular effects mediated via activation of PPAR- and systemic effects on BP that could be in part PPAR- independent and unrelated to the renin-angiotensin-aldosterone system.23 TZDs are insulin-sensitizing agents and may exert water- and salt-retaining effects,24,25 and they could have other renal actions26 that contribute to BP elevation. In our previous study,27 PPAR- expression increased with age during development of hypertension, whereas it did not change in the present study in Ang II–infused rats despite the BP rise. Thus, expression of vascular PPAR- may have effects on vascular remodeling in hypertension that are independent of BP levels.
Pioglitazone and rosiglitazone protect against impairment of endothelial function associated with insulin resistance.9,10 Mechanisms whereby TZDs improved endothelial dysfunction of resistance arteries of Ang II–infused rats could include attenuation of Ang II–induced oxidative stress28,29 secondary to downregulation of AT1 receptors, resulting in less nitric oxide degradation. We recently observed that pioglitazone and rosiglitazone decreased oxidative stress in blood vessels of Ang II–infused rats (unpublished data). An effect on agonist-mediated calcium uptake into VSMCs,10 which would tilt the balance of constriction and relaxation in favor of the latter, could also play a role. Decreased BP could also contribute to improvement of endothelial dysfunction, but hydralazine, which lowered BP, had no effect in the present experiments, which suggests that BP lowering did not participate importantly in these findings.
Expression of PPAR- was thought to be limited primarily to adipose tissue and regulation of lipid metabolism. However, in the present study, neither of the TZDs had any effect on plasma cholesterol, triacylglycerol, or free fatty acid concentrations. Inflammation is an important mechanism in the progression of atherosclerosis. PPAR- activators blunt macrophage activation, as demonstrated by inhibition of gelatinase B (MMP-9), inducible nitric oxide synthase activity, and tumor necrosis factor-
release.6,30 Activation of PPAR- in human endothelial cells can inhibit cell proliferation, modulate plasminogen activator inhibitor-1 expression, reduce endothelin-1 production, and induce apoptosis.31 Endothelial cell PPAR- activation may inhibit activator protein-1 and NF-B pathways that regulate expression of adhesion molecules. PPAR- activators may protect the vasculature by inhibiting the migration of monocytes into the vessel wall through inhibition of upregulation of adhesion molecules.32 In the present study, both PPAR- agonists abrogated upregulation of transcription factor NF-B and adhesion molecules, in agreement with previous reports.6,33
Our results have important implications for the clinical use of PPAR- ligands. In addition to playing a role in adipocyte differentiation, we demonstrate that TZDs have direct effects on the vascular wall. These vascular effects could be PPAR- mediated or PPAR- independent.34 Together with evidence that dominant negative mutations in human PPAR- are associated not only with severe insulin resistance and diabetes mellitus but also with hypertension,35 this suggests that use of TZDs to activate PPAR- may represent an approach to protect the vasculature in hypertension. TZDs may be promising therapeutic agents not only to control metabolic abnormalities in diabetes but also for prevention and/or treatment of hypertension, particularly when associated with insulin resistance or diabetes mellitus.
|
Acknowledgments |
|---|
This work was supported by grant 13570 (to Dr Schiffrin) and a group grant to the Multidisciplinary Research Group on Hypertension, both from the Canadian Institutes of Health Research (CIHR). Dr Diep was supported by a postdoctoral fellowship from CIHR. We are grateful to Suzanne Diebold, Marie-France Lavoie, André Turgeon, and Karim Benkirane for excellent technical assistance.
Received December 28, 2001; revision received February 21, 2002; accepted February 21, 2002.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
1. Carretero OA, Oparil S. Essential hypertension, part I: definition and etiology. Circulation. 2000; 101: 329–335.
2.
Lehmann JM, Moore LB, Smith-Oliver TA, et al. An antidiabetic thiazolidinedione is a high affinity ligand for PPAR-. J Biol Chem. 1995; 270: 12953–12956.
3. Issemann I, Prince RA, Tugwood JD, et al. The retinoid X receptor enhances the function of the PPAR. Biochimie. 1993; 75: 251–256.[Medline] [Order article via Infotrieve]
4.
Marx N, Bourcier T, Sukhova GK, et al. PPAR- activation in human endothelial cells increases plasminogen activator inhibitor type-1 expression: PPAR- as a potential mediator in vascular disease. Arterioscler Thromb Vasc Biol. 1999; 19: 546–551.
5.
Marx N, Schonbeck U, Lazar MA, et al. PPAR- activators inhibit gene expression and migration in human vascular smooth muscle cells. Circ Res. 1998; 83: 1097–1103.
6.
Marx N, Sukhova G, Murphy C, et al. Macrophages in human atheroma contain PPAR-: differentiation-dependent PPAR- expression and reduction of MMP-9 activity through PPAR- activation in mononuclear phagocytes in vitro. Am J Pathol. 1998; 153: 17–23.
7.
Griffin SA, Brown WCB, Macpherson F, et al. Angiotensin II causes vascular hypertrophy in part by a non-pressor mechanism. Hypertension. 1991; 17: 626–635.
8.
Intengan HD, Schiffrin EL. Vascular remodeling in hypertension: roles of apoptosis, inflammation and fibrosis. Hypertension. 2001; 38(pt 2): 581–587.
9. Walker AB, Chattington PD, Buckingham RE, et al. The thiazolidinedione rosiglitazone (BRL-49653) lowers blood pressure and protects against impairment of endothelial function in Zucker fatty rats. Diabetes. 1999; 48: 1448–1453.[Abstract]
10. Buchanan TA, Meehan WP, Jeng YY, et al. Blood pressure lowering by pioglitazone: evidence for a direct vascular effect. J Clin Invest. 1995; 96: 354–360.
11.
Schiffrin EL, Park J-B, Intengan HD, et al. Correction of arterial structure and endothelial dysfunction in human essential hypertension by the angiotensin receptor antagonist losartan. Circulation. 2000; 101: 1653–1659.
12.
Diep QN, El Mabrouk M, Touyz RM, et al. Expression of cell cycle proteins in blood vessels of angiotensin II-infused rats: role of AT(1) receptors. Hypertension. 2001; 37: 604–608.
13.
Muller DN, Mervaala EM, Schmidt F, et al. Effect of bosentan on NF-kappaB, inflammation, and tissue factor in angiotensin II-induced end-organ damage. Hypertension. 2000; 36: 282–290.
14. Schiffrin EL, Thome FS, Genest J. Vascular angiotensin II receptors in renal and DOCA-salt hypertensive rats. Hypertension. 1983; 5(pt 3): V16–V21.
15.
Takeda K, Ichiki T, Tokunou T, et al. Peroxisome proliferator-activated receptor gamma activators downregulate angiotensin II type 1 receptor in vascular smooth muscle cells. Circulation. 2000; 102: 1834–1839.
16.
Sugawara A, Takeuchi K, Uruno A, et al. Transcriptional suppression of type 1 angiotensin II receptor gene expression by PPAR- in vascular smooth muscle cells. Endocrinology. 2001; 142: 3125–3134.
17. Sugawara A, Takeuchi K, Uruno A, et al. Differential effects among thiazolidinediones on the transcription of thromboxane receptor and angiotensin II type 1 receptor genes. Hypertens Res. 2001; 24: 229–233.[CrossRef][Medline] [Order article via Infotrieve]
18. Graf K, Xi XP, Hsueh WA, et al. Troglitazone inhibits angiotensin II-induced DNA synthesis and migration in vascular smooth muscle cells. FEBS Lett. 1997; 400: 119–121.[CrossRef][Medline] [Order article via Infotrieve]
19.
Wakino S, Kintscher U, Kim S, et al. PPAR- ligands inhibit retinoblastoma phosphorylation and G1
S transition in vascular smooth muscle cells. J Biol Chem. 2000; 275: 22435–22441.
20.
Touyz RM, He G, El Mabrouk M, et al. p38 MAP kinase regulates vascular smooth muscle cell collagen synthesis by angiotensin II in SHR but not in WKY. Hypertension. 2001; 37: 574–580.
21. Mulvany MJ, Baumbach GL, Aalkjaer C, et al. Vascular remodeling. Hypertension. 1996; 28: 505–506.
22. Park JB, Schiffrin EL. Effects of antihypertensive therapy on hypertensive vascular disease. Curr Hypertens Rep. 2000; 2: 280–288.[Medline] [Order article via Infotrieve]
23.
Buckingham RE, Al-Barazanji KA, Toseland CD, et al. PPAR- agonist, rosiglitazone, protects against nephropathy and pancreatic islet abnormalities in Zucker fatty rats. Diabetes. 1998; 47: 1326–1334.[Abstract]
24. DeFronzo RA, Cooke CR, Andres R, et al. The effect of insulin on renal handling of sodium, potassium, calcium, and phosphate in man. J Clin Invest. 1975; 55: 845–855.
25. Stenvinkel P, Bolinder J, Alvestrand A. Effects of insulin on renal haemodynamics and the proximal and distal tubular sodium handling in healthy subjects. Diabetologia. 1992; 35: 1042–1048.[CrossRef][Medline] [Order article via Infotrieve]
26. Guan Y, Breyer MD. PPARs: novel therapeutic targets in renal disease. Kidney Int. 2001; 60: 14–30.[CrossRef][Medline] [Order article via Infotrieve]
27.
Diep QN, Schiffrin EL. Increased expression of PPAR- and - in blood vessels of spontaneously hypertensive rats. Hypertension. 2001; 38: 249–254.
28.
Griendling KK, Minieri CA, Ollerenshaw JD, et al. Angiotensin II stimulates NADH and NADPH oxidase activity in cultured vascular smooth muscle cells. Circ Res. 1994; 74: 1141–1148.
29.
Huraux C, Makita T, Kurz S, et al. Superoxide production, risk factors, and endothelium-dependent relaxations in human internal mammary arteries. Circulation. 1999; 99: 53–59.
30.
Ricote M, Li AC, Willson TM, et al. The PPAR- is a negative regulator of macrophage activation. Nature. 1998; 391: 79–82.[CrossRef][Medline]
[Order article via Infotrieve]
31.
Delerive P, Martin-Nizard F, Chinetti G, et al. PPARs inhibit thrombin-induced endothelin-1 production in human vascular endothelial cells by inhibiting the activator protein-1 signaling pathway. Circ Res. 1999; 85: 394–402.
32.
Jackson SM, Parhami F, Xi XP, et al. PPAR activators target human endothelial cells to inhibit leukocyte-endothelial cell interaction. Arterioscler Thromb Vasc Biol. 1999; 19: 2094–2104.
33.
Goetze S, Xi XP, Kawano H, et al. PPAR- ligands inhibit migration mediated by multiple chemoattractants in vascular smooth muscle cells. J Cardiovasc Pharmacol. 1999; 33: 798–806.[CrossRef][Medline]
[Order article via Infotrieve]
34.
Chawla A, Barak Y, Nagy L, et al. PPAR- dependent and independent effects on macrophage-gene expression in lipid metabolism and inflammation. Nat Med. 2001; 7: 48–52.[CrossRef][Medline]
[Order article via Infotrieve]
35. Barroso I, Gurnell M, Crowley VEF, et al. Dominant negative mutations in human PPARgamma associated with severe insulin resistance, diabetes mellitus and hypertension. Nature. 1999; 402: 880–883.[Medline] [Order article via Infotrieve]
This article has been cited by other articles:
 |
|
 |
|
  Y.-S. Tsai, L. Xu, O. Smithies, and N. Maeda Genetic variations in peroxisome proliferator-activated receptor {gamma} expression affect blood pressure PNAS, November 10, 2009; 106(45): 19084 - 19089. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Kleinhenz, D. J. Kleinhenz, S. You, J. D. Ritzenthaler, J. M. Hansen, D. R. Archer, R. L. Sutliff, and C. M. Hart Disruption of endothelial peroxisome proliferator-activated receptor-{gamma} reduces vascular nitric oxide production Am J Physiol Heart Circ Physiol, November 1, 2009; 297(5): H1647 - H1654. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Verlohren, D. N. Muller, F. C. Luft, and R. Dechend Immunology in Hypertension, Preeclampsia, and Target-Organ Damage Hypertension, September 1, 2009; 54(3): 439 - 443. [Full Text] [PDF]
|
|
|
|
 |
|
 P. S. Chaggar, S. M. Shaw, and S. G. Williams Review article: Thiazolidinediones and heart failure Diabetes and Vascular Disease Research, July 1, 2009; 6(3): 146 - 152. [Abstract] [PDF]
|
|
|
|
 |
|
 A. Jones, R. Deb, E. Torsney, F. Howe, M. Dunkley, Y. Gnaneswaran, D. Gaze, H. Nasr, I. M. Loftus, M. M. Thompson, et al. Rosiglitazone Reduces the Development and Rupture of Experimental Aortic Aneurysms Circulation, June 23, 2009; 119(24): 3125 - 3132. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Chang, L. Villacorta, J. Zhang, M. T. Garcia-Barrio, K. Yang, M. Hamblin, S. E. Whitesall, L. G. D'Alecy, and Y. E. Chen Vascular Smooth Muscle Cell-Selective Peroxisome Proliferator-Activated Receptor-{gamma} Deletion Leads to Hypotension Circulation, April 28, 2009; 119(16): 2161 - 2169. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Venegas-Pont, J. C. Sartori-Valinotti, C. Maric, L. C. Racusen, P. H. Glover, G. R. McLemore Jr., A. V. Jones, J. F. Reckelhoff, and M. J. Ryan Rosiglitazone decreases blood pressure and renal injury in a female mouse model of systemic lupus erythematosus Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2009; 296(4): R1282 - R1289. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. L. Schiffrin and P. Paradis Suppression of Peroxisome Proliferator-Activated Receptor-{gamma} Activity by Angiotensin II in Vascular Smooth Muscle Involves Bcr Kinase: The Fire That Drowns The Water Circ. Res., January 2, 2009; 104(1): 4 - 6. [Full Text] [PDF]
|
|
|
|
 |
|
 N. Wang, J. D. Symons, H. Zhang, Z. Jia, F. J. Gonzalez, and T. Yang Distinct Functions of Vascular Endothelial and Smooth Muscle PPAR{gamma} in Regulation of Blood Pressure and Vascular Tone Toxicol Pathol, January 1, 2009; 37(1): 21 - 27. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Siekmeier, T. Grammer, and W. Marz Roles of Oxidants, Nitric Oxide, and Asymmetric Dimethylarginine in Endothelial Function Journal of Cardiovascular Pharmacology and Therapeutics, December 1, 2008; 13(4): 279 - 297. [Abstract] [PDF]
|
|
|
|
|
|
A. M. Beyer, W. J. de Lange, C. M. Halabi, M. L. Modrick, H. L. Keen, F. M. Faraci, and C. D. Sigmund Endothelium-Specific Interference With Peroxisome Proliferator Activated Receptor Gamma Causes Cerebral Vascular Dysfunction in Response to a High-Fat Diet Circ. Res., September 12, 2008; 103(6): 654 - 661. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Nicolakakis, T. Aboulkassim, B. Ongali, C. Lecrux, P. Fernandes, P. Rosa-Neto, X.-K. Tong, and E. Hamel Complete Rescue of Cerebrovascular Function in Aged Alzheimer's Disease Transgenic Mice by Antioxidants and Pioglitazone, a Peroxisome Proliferator-Activated Receptor {gamma} Agonist J. Neurosci., September 10, 2008; 28(37): 9287 - 9296. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. L. Schiffrin The Flame That Lights the Fire: Oxidative Stress, Inflammation, and Renal Damage in Angiotensin II-Induced Hypertension Hypertension, August 1, 2008; 52(2): 205 - 206. [Full Text] [PDF]
|
|
|
|
|
|
I. Kuipers, P. van der Harst, G. Navis, L. van Genne, F. Morello, W. H. van Gilst, D. J. van Veldhuisen, and R. A. de Boer Nuclear Hormone Receptors as Regulators of the Renin-Angiotensin-Aldosterone System Hypertension, June 1, 2008; 51(6): 1442 - 1448. [Full Text] [PDF]
|
|
|
|
 |
|
 X. Ruan, F. Zheng, and Y. Guan PPARs and the kidney in metabolic syndrome Am J Physiol Renal Physiol, May 1, 2008; 294(5): F1032 - F1047. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. M. Faraci Surviving the Remodel: The Impact of Hypertension During Pregnancy Hypertension, April 1, 2008; 51(4): 995 - 996. [Full Text] [PDF]
|
|
|
|
|
|
A. M. Beyer, G. L. Baumbach, C. M. Halabi, M. L. Modrick, C. M. Lynch, T. D. Gerhold, S. M. Ghoneim, W. J. de Lange, H. L. Keen, Y.-S. Tsai, et al. Interference With PPAR{gamma} Signaling Causes Cerebral Vascular Dysfunction, Hypertrophy, and Remodeling Hypertension, April 1, 2008; 51(4): 867 - 871. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Z. Duan, M. G. Usher, and R. M. Mortensen Peroxisome Proliferator-Activated Receptor-{gamma}-Mediated Effects in the Vasculature Circ. Res., February 15, 2008; 102(3): 283 - 294. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. T. Weatherford, H. Itani, H. L. Keen, and C. D. Sigmund Is Peroxisome Proliferator-Activated Receptor-{gamma} a New "Pal" of Renin? Hypertension, November 1, 2007; 50(5): 844 - 846. [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Socha, M. Manhiani, N. Said, J. D. Imig, and K. Motamed Secreted Protein Acidic and Rich in Cysteine Deficiency Ameliorates Renal Inflammation and Fibrosis in Angiotensin Hypertension Am. J. Pathol., October 1, 2007; 171(4): 1104 - 1112. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. S. Elton and M. M. Martin Angiotensin II Type 1 Receptor Gene Regulation: Transcriptional and Posttranscriptional Mechanisms Hypertension, May 1, 2007; 49(5): 953 - 961. [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]
|
|
|
|
 |
|
 M. A. Potenza, F. L. Marasciulo, M. Tarquinio, M. J. Quon, and M. Montagnani Treatment of Spontaneously Hypertensive Rats With Rosiglitazone and/or Enalapril Restores Balance Between Vasodilator and Vasoconstrictor Actions of Insulin With Simultaneous Improvement in Hypertension and Insulin Resistance Diabetes, December 1, 2006; 55(12): 3594 - 3603. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Zanchi, C. Perregaux, M. Maillard, D. Cefai, J. Nussberger, and M. Burnier The PPAR{gamma} agonist pioglitazone modifies the vascular sodium-angiotensin II relationship in insulin-resistant rats Am J Physiol Endocrinol Metab, December 1, 2006; 291(6): E1228 - E1234. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Imayama, T. Ichiki, K. Inanaga, H. Ohtsubo, K. Fukuyama, H. Ono, Y. Hashiguchi, and K. Sunagawa Telmisartan downregulates angiotensin II type 1 receptor through activation of peroxisome proliferator-activated receptor {gamma} Cardiovasc Res, October 1, 2006; 72(1): 184 - 190. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Molavi, J. Chen, and J. L. Mehta Cardioprotective effects of rosiglitazone are associated with selective overexpression of type 2 angiotensin receptors and inhibition of p42/44 MAPK Am J Physiol Heart Circ Physiol, August 1, 2006; 291(2): H687 - H693. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Paul, A. Poyan Mehr, and R. Kreutz Physiology of local Renin-Angiotensin systems. Physiol Rev, July 1, 2006; 86(3): 747 - 803. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. M.A.C. Martens, T. J. Rabelink, J. op 't Roodt, E. J.P. de Koning, and F. L.J. Visseren TNF-{alpha} induces endothelial dysfunction in diabetic adults, an effect reversible by the PPAR-{gamma} agonist pioglitazone Eur. Heart J., July 1, 2006; 27(13): 1605 - 1609. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Weissgarten, S. Berman, S. Efrati, M. Rapoport, Z. Averbukh, and L. Feldman Apoptosis and proliferation of cultured mesangial cells isolated from kidneys of rosiglitazone-treated pregnant diabetic rats Nephrol. Dial. Transplant., May 1, 2006; 21(5): 1198 - 1204. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Hermann and F. Ruschitzka Novel anti-inflammatory drugs in hypertension Nephrol. Dial. Transplant., April 1, 2006; 21(4): 859 - 864. [Full Text] [PDF]
|
|
|
|
|
|
K. Benkirane, F. Amiri, Q. N. Diep, M. El Mabrouk, and E. L. Schiffrin PPAR-{gamma} inhibits ANG II-induced cell growth via SHIP2 and 4E-BP1 Am J Physiol Heart Circ Physiol, January 1, 2006; 290(1): H390 - H397. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Benkirane, E. C. Viel, F. Amiri, and E. L. Schiffrin Peroxisome Proliferator-Activated Receptor {gamma} Regulates Angiotensin II-Stimulated Phosphatidylinositol 3-Kinase and Mitogen-Activated Protein Kinase in Blood Vessels In Vivo Hypertension, January 1, 2006; 47(1): 102 - 108. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. L. Schiffrin More Evidence of Cardiorenal Protective Effects of Peroxisome Proliferator-Activated Receptor Activation Hypertension, August 1, 2005; 46(2): 267 - 268. [Full Text] [PDF]
|
|
|
|
|
|
H. Zhang, A. Zhang, D. E. Kohan, R. D. Nelson, F. J. Gonzalez, and T. Yang Collecting duct-specific deletion of peroxisome proliferator-activated receptor {gamma} blocks thiazolidinedione-induced fluid retention PNAS, June 28, 2005; 102(26): 9406 - 9411. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. J. Zieman, V. Melenovsky, and D. A. Kass Mechanisms, Pathophysiology, and Therapy of Arterial Stiffness Arterioscler Thromb Vasc Biol, May 1, 2005; 25(5): 932 - 943. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. C. Blaxall, J. M. Miano, and B. C. Berk Angiotensin II: A Devious Activator of Mineralocorticoid Receptor-Dependent Gene Expression Circ. Res., April 1, 2005; 96(6): 610 - 611. [Full Text] [PDF]
|
|
|
|
|
|
E. L. Schiffrin Peroxisome proliferator-activated receptors and cardiovascular remodeling Am J Physiol Heart Circ Physiol, March 1, 2005; 288(3): H1037 - H1043. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Guan Peroxisome Proliferator-Activated Receptor Family and Its Relationship to Renal Complications of the Metabolic Syndrome J. Am. Soc. Nephrol., November 1, 2004; 15(11): 2801 - 2815. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Amiri, A. Virdis, M. F. Neves, M. Iglarz, N. G. Seidah, R. M. Touyz, T. L. Reudelhuber, and E. L. Schiffrin Endothelium-Restricted Overexpression of Human Endothelin-1 Causes Vascular Remodeling and Endothelial Dysfunction Circulation, October 12, 2004; 110(15): 2233 - 2240. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Chen, A.-P. Arrigo, and R. W. Currie Heat shock treatment suppresses angiotensin II-induced activation of NF-{kappa}B pathway and heart inflammation: a role for IKK depletion by heat shock? Am J Physiol Heart Circ Physiol, September 1, 2004; 287(3): H1104 - H1114. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. H. Endemann and E. L. Schiffrin Endothelial Dysfunction J. Am. Soc. Nephrol., August 1, 2004; 15(8): 1983 - 1992. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. L. Schiffrin and R. M. Touyz From bedside to bench to bedside: role of renin-angiotensin-aldosterone system in remodeling of resistance arteries in hypertension Am J Physiol Heart Circ Physiol, August 1, 2004; 287(2): H435 - H446. [Full Text] [PDF]
|
|
|
|
|
|
D. J. Kelly, A. J. Cox, R. M. Gow, Y. Zhang, B. E. Kemp, and R. E. Gilbert Platelet-Derived Growth Factor Receptor Transactivation Mediates the Trophic Effects of Angiotensin II In Vivo Hypertension, August 1, 2004; 44(2): 195 - 202. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. L. Keen, M. J. Ryan, A. Beyer, S. Mathur, T. E. Scheetz, B. D. Gackle, F. M. Faraci, T. L. Casavant, and C. D. Sigmund Gene expression profiling of potential PPAR{gamma} target genes in mouse aorta Physiol Genomics, June 17, 2004; 18(1): 33 - 42. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Natali, S. Baldeweg, E. Toschi, B. Capaldo, D. Barbaro, A. Gastaldelli, J. S. Yudkin, and E. Ferrannini Vascular Effects of Improving Metabolic Control With Metformin or Rosiglitazone in Type 2 Diabetes Diabetes Care, June 1, 2004; 27(6): 1349 - 1357. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Marx, H. Duez, J.-C. Fruchart, and B. Staels Peroxisome Proliferator-Activated Receptors and Atherogenesis: Regulators of Gene Expression in Vascular Cells Circ. Res., May 14, 2004; 94(9): 1168 - 1178. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. P.H. van Wijk and T. J. Rabelink PPAR-{gamma} Agonists: Shifting Attention from the Belly to the Heart? Arterioscler Thromb Vasc Biol, May 1, 2004; 24(5): 798 - 800. [Full Text]
|
|
|
|
 |
|
 A. Zanchi, A. Chiolero, M. Maillard, J. Nussberger, H.-R. Brunner, and M. Burnier Effects of the Peroxisomal Proliferator-Activated Receptor-{gamma} Agonist Pioglitazone on Renal and Hormonal Responses to Salt in Healthy Men J. Clin. Endocrinol. Metab., March 1, 2004; 89(3): 1140 - 1145. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Ryan, S. P. Didion, S. Mathur, F. M. Faraci, and C. D. Sigmund PPAR{gamma} Agonist Rosiglitazone Improves Vascular Function and Lowers Blood Pressure in Hypertensive Transgenic Mice Hypertension, March 1, 2004; 43(3): 661 - 666. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Pistrosch, J. Passauer, S. Fischer, K. Fuecker, M. Hanefeld, and P. Gross In Type 2 Diabetes, Rosiglitazone Therapy for Insulin Resistance Ameliorates Endothelial Dysfunction Independent of Glucose Control Diabetes Care, February 1, 2004; 27(2): 484 - 490. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. H. Endemann, Q. Pu, C. De Ciuceis, C. Savoia, A. Virdis, M. F. Neves, R. M. Touyz, and E. L. Schiffrin Persistent Remodeling of Resistance Arteries in Type 2 Diabetic Patients on Antihypertensive Treatment Hypertension, February 1, 2004; 43(2): 399 - 404. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. A. Hsueh and D. Bruemmer Peroxisome Proliferator-Activated Receptor {gamma}: Implications for Cardiovascular Disease Hypertension, February 1, 2004; 43(2): 297 - 305. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. R. Mehrabi, P. Haslmayer, S. Humpeler, G. Strauss-Blasche, W. Marktl, F. Tamaddon, N. Serbecic, G. Wieselthaler, T. Thalhammer, H. D. Glogar, et al. Quantitative analysis of peroxisome proliferator-activated receptor gamma (PPAR{gamma}) expression in arteries and hearts of patients with ischaemic or dilated cardiomyopathy Eur J Heart Fail, December 1, 2003; 5(6): 733 - 739. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. S. Sidhu, D. Cowan, and J.-C. Kaski The effects of rosiglitazone, a peroxisome proliferator-activated receptor-gamma agonist, on markers of endothelial cell activation, C-reactive protein, and fibrinogen levels in non-diabetic coronary artery disease patients J. Am. Coll. Cardiol., November 19, 2003; 42(10): 1757 - 1763. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Mae, H. Kishida, T. Nishiyama, M. Tsukagawa, E. Konishi, M. Kuroda, Y. Mimaki, Y. Sashida, K. Takahashi, T. Kawada, et al. A Licorice Ethanolic Extract with Peroxisome Proliferator-Activated Receptor-{gamma} Ligand-Binding Activity Affects Diabetes in KK-Ay Mice, Abdominal Obesity in Diet-Induced Obese C57BL Mice and Hypertension in Spontaneously Hypertensive Rats J. Nutr., November 1, 2003; 133(11): 3369 - 3377. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Iglarz, R. M. Touyz, E. C. Viel, P. Paradis, F. Amiri, Q. N. Diep, and E. L. Schiffrin Peroxisome Proliferator-Activated Receptor-{alpha} and Receptor-{gamma} Activators Prevent Cardiac Fibrosis in Mineralocorticoid-Dependent Hypertension Hypertension, October 1, 2003; 42(4): 737 - 743. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. L. Schiffrin, F. Amiri, K. Benkirane, M. Iglarz, and Q. N. Diep Peroxisome Proliferator-Activated Receptors: Vascular and Cardiac Effects in Hypertension Hypertension, October 1, 2003; 42(4): 664 - 668. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. L. Schiffrin and R. M. Touyz Multiple actions of angiotensin II in hypertension: benefits of AT1 receptor blockade J. Am. Coll. Cardiol., September 3, 2003; 42(5): 911 - 913. [Full Text] [PDF]
|
|
|
|
 |
|
 F. Liang, F. Wang, S. Zhang, and D. G. Gardner Peroxisome Proliferator Activated Receptor (PPAR){alpha} Agonists Inhibit Hypertrophy of Neonatal Rat Cardiac Myocytes Endocrinology, September 1, 2003; 144(9): 4187 - 4194. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. Lemarie, B. Esposito, A. Tedgui, and S. Lehoux Pressure-Induced Vascular Activation of Nuclear Factor-{kappa}B: Role in Cell Survival Circ. Res., August 8, 2003; 93(3): 207 - 212. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Virdis, M. Iglarz, M. F. Neves, F. Amiri, R. M. Touyz, R. Rozen, and E. L. Schiffrin Effect of Hyperhomocystinemia and Hypertension on Endothelial Function in Methylenetetrahydrofolate Reductase-Deficient Mice Arterioscler Thromb Vasc Biol, August 1, 2003; 23(8): 1352 - 1357. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-H. Wang, R. D. Weisel, P. P. Liu, P. W.M. Fedak, and S. Verma Glitazones and Heart Failure: Critical Appraisal for the Clinician Circulation, March 18, 2003; 107(10): 1350 - 1354. [Full Text] [PDF]
|
|
|
|
 |
|
 H. Funke-Kaiser, F. Reichenberger, K. Kopke, S.-M. Herrmann, J. Pfeifer, H.-D. Orzechowski, W. Zidek, M. Paul, and E. Brand Differential binding of transcription factor E2F-2 to the endothelin-converting enzyme-1b promoter affects blood pressure regulation Hum. Mol. Genet., February 15, 2003; 12(4): 423 - 433. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Castoldi, C. R. T. di Gioia, F. Pieruzzi, C. D'Orlando, W. M. M. van de Greef, G. Busca, G. Sperti, and A. Stella ANG II increases TIMP-1 expression in rat aortic smooth muscle cells in vivo Am J Physiol Heart Circ Physiol, February 1, 2003; 284(2): H635 - H643. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Iglarz, R. M. Touyz, F. Amiri, M.-F. Lavoie, Q. N. Diep, and E. L. Schiffrin Effect of Peroxisome Proliferator-Activated Receptor-{alpha} and -{gamma} Activators on Vascular Remodeling in Endothelin-Dependent Hypertension Arterioscler Thromb Vasc Biol, January 1, 2003; 23(1): 45 - 51. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. N. Diep, F. Amiri, R. M. Touyz, J. S. Cohn, D. Endemann, M. F. Neves, and E. L. Schiffrin PPAR{alpha} Activator Effects on Ang II-Induced Vascular Oxidative Stress and Inflammation Hypertension, December 1, 2002; 40(6): 866 - 871. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||