RT Journal Article
SR Electronic
T1 A Dietary Agonist of Transient Receptor Potential Cation Channel V3 Elicits Endothelium-Dependent Vasodilation
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 612
OP 620
DO 10.1124/mol.109.060715
VO 77
IS 4
A1 Scott Earley
A1 Albert L. Gonzales
A1 Zarine I. Garcia
YR 2010
UL http://molpharm.aspetjournals.org/content/77/4/612.abstract
AB The Mediterranean diet may be responsible for lower cardiovascular disease rates in Southern versus Northern European countries. Oregano is used abundantly in Mediterranean cooking, but potential cardiovascular benefits have not been investigated. Carvacrol, present in oregano, activates the transient receptor potential (TRP) cation channels TRPA1 and TRPV3. We hypothesized that chemosensing of this dietary molecule by TRP channels in the endothelium promotes arterial relaxation. TRPA1 and TRPV3 were detected in the endothelium of intact arteries. Carvacrol causes concentration-dependent increases in the intracellular [Ca2+] of native cerebral artery endothelial cells and is more potent (EC50 = 34 μM) than the TRPA1 agonist allyl isothiocyanate (EC50 = 400 μM) or the TRPV3 agonist eugenol (EC50 = 2.3 mM). Carvacrol also activates TRPV3-like cation currents in cerebral artery endothelial cells. Carvacrol elicits vasodilation of intact cerebral arteries (EC50 = 4.1 μM) that is accompanied by smooth muscle hyperpolarization and a decrease in the intracellular [Ca2+] of arterial myocytes. Endothelium disruption inhibits carvacrol-induced vasodilation, but block of nitric-oxide synthase and cyclooxygenase activity does not alter the response. Vasodilation in response to carvacrol is inhibited when blockers of Ca2+-activated K+ channels are present in the lumen or when the inwardly rectifying K+ channel blocker BaCl2 is present in the superfusion bath. Carvacrol-induced dilation is not diminished by a TRPA1 antagonist but is inhibited by the TRPV blocker ruthenium red. Our findings show that oregano can relax arteries by activating TRPV3 channels in the endothelium. This effect may account for some of the cardioprotective effects of the Mediterranean diet.Copyright © 2010 The American Society for Pharmacology and Experimental Therapeutics