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KMID : 0648320080140030004
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Journal of The Korean Society of Hypertension
2008 Volume.14 No. 3 p.4 ~ p.11
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Effects of Peroxisome Proliferator-Activated Receptors gamma Agonist on Aortic vascular Function in Spontaneous Hypertensive Rats
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Lee Sook-Jin
Seo Jung-Won
Kim Kwang-Il
Chang Hyuk-Jae
Cho Young-Seok
Youn Tae-Jin
Chae In-Ho
Kim Cheol-Ho
Choi Dong-Ju
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Abstract
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Background : Hypertension is associated with endothelial dysfunction, which may contribute to increased cardiovascular risk. Caveolin-1, in the endothelium, regulates nitric oxide signaling by binding to and inhibiting endothelial nitric oxide synthase (eNOS). The purpose of this study was to examine whether Peroxisome Proliferator-Activated Receptors gamma (PPAR-γ agonist, pioglitazone) may alleviate impaired endothelial-dependent dilatation of the aorta in Spontaneous Hypertensive Rat(SHR) and to determine the underlying mechanisms involved.
Methods : Twelve-week-old male SHR were assigned to piglitazone (PIO) or control (CON) groups. Pioglitazone (10 mg/kg/d) or placebo was administered mixed with chow for 8 weeks. And abdominal aortic rings were prepared and vascular responses to acetylcholine (10-9~10-4 M) were determined in vitro. To evaluate the potential role of nitric oxide and caveolin-1 in vasodilatation in the CON and PIO group, we examined the plasma activity of Nitrate/nitrite and expression of eNOS and caveolin-1 in the rat aorta.
Results : PPAR-γ agonist, without affecting blood pressure and blood glucose values, improved the hypertension-induced reduction in endothelium-dependent vasodilation in aortic preparations. Expression of eNOS RNA
in aorta was unchanged by pioglitazone, whereas plasma Nitrate/nitrite level was increased by ?2 times, while caveolin-1 expression was decreased.
Conclusions : We conclude that PPAR-γ agonist can improve impaired endothelium-dependent dilatation of aorta by high blood pressure by altering eNOS subcellular distribution and its association with inhibitory proteins, caveolin-1. These results imply the insight of novel mechanisms of pathogenesis and the design of clinical strategies that approach the high blood pressure-associated loss of NO availability and endothelial dysfunction by targeting the pathway.
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KEYWORD
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endothelial function, PPAR-γ agonist, nitric oxide, Spontaneous hypertensive rat
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