Impaired capsaicin-induced relaxation of coronary arteries in a porcine model of the metabolic syndrome.
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 microM). TRPV1 immunoreactivity was prominent in coronary endothelial cells. TRPV1 protein expression was decreased 40 +/- 11% in obese pigs. Capsaicin (100 microM) 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.
Bratz
Ian N
IN
Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, Indiana 46202-5120, USA. ibratz@iupui.edu
Dick
Gregory M
GM
Tune
Johnathan D
JD
Edwards
Jason M
JM
Neeb
Zachary P
ZP
Dincer
U Deniz
UD
Sturek
Michael
M
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology*; D003331:Coronary Vessels / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D008345:Manganese / Q000378:metabolism; D024821:Metabolic Syndrome / Q000378:metabolism / Q000503:physiopathology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D013552:Swine; D013556:Swine, Miniature; D050916:TRPV Cation Channels / Q000819:agonists* / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D014665:Vasodilator Agents; D009569:Nitric Oxide; D008345:Manganese; D019001:Nitric Oxide Synthase; C071423:capsazepine; D002211:Capsaicin; D002118:Calcium