Document Detail

Nifedipine activates PPARgamma and exerts antioxidative action through Cu/ZnSOD independent of blood-pressure lowering in SHRSP.
MedLine Citation:
PMID:  20460829     Owner:  NLM     Status:  MEDLINE    
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 PPARgamma, inhibits vascular remodeling, and improves vascular function in hypertension.
METHODS: Stroke-prone spontaneously hypertensive rats (SHRSP) were treated with vehicle, nifedipine, and PPARgamma 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 PPARgamma and Cu/ZnSOD expression/activities to their levels in the WKY rat heart. Furthermore, nifedipine induced a dose-dependent increase in PPARgamma 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 PPARgamma through the activation of Cu/ZnSOD in hypertension.
Ryo Hashimoto; Seiji Umemoto; Fengling Guo; Kyoko Umeji; Shinichi Itoh; Hiroko Kishi; Sei Kobayashi; Masunori Matsuzaki
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-05-07
Journal Detail:
Title:  Journal of atherosclerosis and thrombosis     Volume:  17     ISSN:  1880-3873     ISO Abbreviation:  J. Atheroscler. Thromb.     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-09-06     Completed Date:  2011-01-04     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9506298     Medline TA:  J Atheroscler Thromb     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  785-95     Citation Subset:  IM    
Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan.
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MeSH Terms
Anilides / pharmacology
Aorta / cytology,  drug effects,  metabolism
Blood Pressure / drug effects*
Calcium Channel Blockers / therapeutic use*
Cells, Cultured
Endothelium, Vascular / drug effects,  metabolism
Hypertension / drug therapy*,  metabolism,  pathology
Mesenteric Arteries / drug effects,  metabolism
Muscle, Smooth, Vascular / drug effects,  metabolism
Nifedipine / therapeutic use*
Oxidative Stress
PPAR gamma / antagonists & inhibitors,  metabolism*
Rats, Inbred SHR
Rats, Inbred WKY
Stroke / drug therapy*,  metabolism,  pathology
Superoxide Dismutase / metabolism*
Superoxides / metabolism
Reg. No./Substance:
0/2-chloro-5-nitrobenzanilide; 0/Anilides; 0/Calcium Channel Blockers; 0/PPAR gamma; 11062-77-4/Superoxides; 21829-25-4/Nifedipine; EC Dismutase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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