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

Ian N. Bratz, Gregory M. Dick, Johnathan Tune, Jason M. Edwards, Zachary P. Neeb, U. Deniz Dincer, Michael Sturek

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Abstract

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.

Original languageEnglish
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume294
Issue number6
DOIs
StatePublished - Jun 2008

Fingerprint

Capsaicin
Coronary Vessels
Swine
Vasodilation
Coronary Circulation
Endothelium
Endothelial Cells
Transient Receptor Potential Channels
Miniature Swine
Divalent Cations
Nitric Oxide Synthase
Blood Vessels
Cations
Nitric Oxide
Arteries
Proteins

Keywords

  • Endothelial cells
  • Nitric oxide
  • Ossabaw miniature swine
  • Potassium channels
  • Transient receptor potential vanilloid 1

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

Cite this

Impaired capsaicin-induced relaxation of coronary arteries in a porcine model of the metabolic syndrome. / Bratz, Ian N.; Dick, Gregory M.; Tune, Johnathan; Edwards, Jason M.; Neeb, Zachary P.; Dincer, U. Deniz; Sturek, Michael.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 294, No. 6, 06.2008.

Research output: Contribution to journalArticle

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