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This Article Full Text Full Text (PDF) All Versions of this Article: 294/6/H2489    most recent 01191.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Bratz, I. N. Articles by Sturek, M. PubMed PubMed Citation Articles by Bratz, I. N. Articles by Sturek, M.

Impaired capsaicin-induced relaxation of coronary arteries in a porcine model of the metabolic syndrome

Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, Indiana

Submitted 12 October 2007 ; accepted in final form 31 March 2008

Recent studies implicate channels of the transient receptor potential vanilloid family (e.g., TRPV1) in regulating vascular tone; however, little is known about these channels in the coronary circulation. Furthermore, it is unclear whether metabolic syndrome alters the function and/or expression of TRPV1. We tested the hypothesis that TRPV1 mediates coronary vasodilation through endothelium-dependent mechanisms that are impaired by the metabolic syndrome. Studies were conducted on coronary arteries from lean and obese male Ossabaw miniature swine. In lean pigs, capsaicin, a TRPV1 agonist, relaxed arteries in a dose-dependent manner (EC₅₀ = 116 ± 41 nM). Capsaicin-induced relaxation was blocked by the TRPV1 antagonist capsazepine, endothelial denudation, inhibition of nitric oxide synthase, and K⁺ channel antagonists. Capsaicin-induced relaxation was impaired in rings from pigs with metabolic syndrome (91 ± 4% vs. 51 ± 10% relaxation at 100 µM). TRPV1 immunoreactivity was prominent in coronary endothelial cells. TRPV1 protein expression was decreased 40 ± 11% in obese pigs. Capsaicin (100 µM) elicited divalent cation influx that was abolished in endothelial cells from obese pigs. These data indicate that TRPV1 channels are functionally expressed in the coronary circulation and mediate endothelium-dependent vasodilation through a mechanism involving nitric oxide and K⁺ channels. Impaired capsaicin-induced vasodilation in the metabolic syndrome is associated with decreased expression of TRPV1 and cation influx.

Ossabaw miniature swine; transient receptor potential vanilloid 1; potassium channels; nitric oxide; endothelial cells