Journal of Atherosclerosis and Thrombosis
Online ISSN : 1880-3873
Print ISSN : 1340-3478
ISSN-L : 1340-3478
Original Article
Nifedipine Activates PPARγ and Exerts Antioxidative Action Through Cu/ZnSOD Independent of Blood-pressure Lowering in SHRSP
Ryo HashimotoSeiji UmemotoFengling GuoKyoko UmejiShinichi ItohHiroko KishiSei KobayashiMasunori Matsuzaki
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JOURNAL OPEN ACCESS

2010 Volume 17 Issue 8 Pages 785-795

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Abstract

Aim: It has been shown that the calcium antagonist nifedipine upregulates superoxide dismutase (SOD). Although the peroxisome proliferator-activated receptor (PPAR) response element is located in the promoter region of Cu/ZnSOD, it remains unclear whether nifedipine upregulates PPARs and inhibits vascular remodeling. We hypothesthized that nifedipine activates PPARγ, inhibits vascular remodeling, and improves vascular function in hypertension.
Methods: Stroke-prone spontaneously hypertensive rats (SHRSP) were treated with vehicle, nifedipine, and PPARγ selective antagonist GW9662 with nifedipine.
Results: Systolic blood pressure in the three SHRSP groups was higher (p <0.01), and the left ventricular weight/body weight ratio was greater (p <0.01) than in the Wistar-Kyoto rat (WKY) group with no differences observed among the three SHRSP groups. In the SHRSP heart, nifedipine significantly inhibited intramyocardial arterial remodeling and perivascular fibrosis, and reduced oxidative stress, while it significantly restored adiponectin and the smooth muscle cell (SMC) phenotype, and selectively restored PPARγ and Cu/ZnSOD expression/activities to their levels in the WKY rat heart. Furthermore, nifedipine induced a dose-dependent increase in PPARγ expression in cultured vascular SMCs. These effects of nifedipine were completely abolished by the co-administration of GW9662 with nifedipine. Nifedipine treatment significantly improved acetylcholine-induced relaxation by 27% compared with the vehicle SHRSP group, but it was still significantly impaired by 20% compared with the WKY group.
Conclusions: Nifedipine may inhibit vascular remodeling and improve vascular function by selective activation of PPARγ through the activation of Cu/ZnSOD in hypertension.

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https://creativecommons.org/licenses/by-nc-sa/4.0/deed.ja
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