Zusammenfassung
Background-Pioglitazone and rosiglitazone, thiazolidinedione peroxisome proliferator-activated receptor-gamma (PPAR-gamma) 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 ...
Zusammenfassung
Background-Pioglitazone and rosiglitazone, thiazolidinedione peroxisome proliferator-activated receptor-gamma (PPAR-gamma) 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 H-3-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-κB activity were increased. These changes were abrogated by pioglitazone or rosiglitazone. Conclusions-Thiazolidinedione PPAR-γ 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.
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