Effect of ethanol on capsaicin-induced nerve-mediated vasorelaxation in rat arteries

Capsaicin, a pungent component of red chili peppers, is a potent vasorelaxant. Although the mechanism of capsaicin-induced relaxation seems to involve binding of capsaicin to the transient receptor potential vanilloid type 1 (TRPV1) cation channel and release of calcitonin gene-related peptide (CGRP) from the sensory nerve terminals, there is little evidence to suggest that capsaicin-induced relaxation is affected by ethanol. Therefore, in this study, we examined the effects of ethanol and several pharmacological antagonists on capsaicin-or CGRP-induced relaxation in rat arteries. Experiments were performed on hepatic and superior mesenteric arteries of male Wistar rats. We measured the isometric tension in the rings of these arteries with their endothelium removed to exclude the influence of the endothelial cells. Then, the arteries precontracted with phenylephrine were exposed to cumulative concentrations of capsaicin or CGRP in the absence or presence of ethanol and several antagonists. Capsaicin and CGRP caused dose-dependent relaxation in both arteries precontracted with phenylephrine. Capsaicin-induced relaxation was significantly inhibited by TRPV1 antagonists capsazepine, ruthenium red and CGRP receptor antagonist CGRP 8-37. Ethanol also significantly inhibited capsaicin-induced relaxation but did not affect CGRP-induced relaxation. Capsaicin-induced relaxation is mediated by the release of CGRP from the sensory nerve terminals via activation of the TRPV1, and ethanol did not inhibit relaxation at the smooth muscle level but inhibited CGRP release from the sensory nerve terminals.