A Dietary Agonist of Transient Receptor Potential Cation Channel V3 Elicits Endothelium-Dependent Vasodilation

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 [Ca(2+)] of native cerebral artery endothelial cells and is more potent (EC(50) = 34 mu M) than the TRPA1 agonist allyl isothiocyanate (EC(50) = 400 mu M) or the TRPV3 agonist eugenol (EC(50) = 2.3 mM). Carvacrol also activates TRPV3-like cation currents in cerebral artery endothelial cells. Carvacrol elicits vasodilation of intact cerebral arteries (EC(50) = 4.1 mu M) that is accompanied by smooth muscle hyperpolarization and a decrease in the intracellular [Ca(2+)] 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 Ca(2+)-activated K(+) channels are present in the lumen or when the inwardly rectifying K(+) channel blocker BaCl(2) 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.