Cannabinoids‐Induced Vasodilation in Rat Mesenteric Artery: Possible Mechanisms of Action

Abstract

Mesenteric artery is a resistance vessel, which has an important function in the arterial pressure maintenance. The vascular tone can be modulated through synthesis and release of vasoactive substances of the endothelium as well as through substances that can cause relaxation or contraction of the arterial smooth muscle. Some of these modulator substances are the cannabinoids. It has been shown that cannabinoids are able to produce changes in the vascular tone through different mechanisms including the activation of the cannabinoid receptors (CB1 and CB2). The aim of this study was to analyze the possible mechanisms through which cannabinoids cause rat mesenteric artery vasodilation. We have done tension experiments using synthetic cannabinoids that are selective agonists for CB1 (ACPA) and CB2 (JWH‐133) receptors, and selective antagonists (AM281 and AM630). The cannabinoids were applied in arterial rings with or without endothelium. The results show that ACPA and JWH‐133 activate cannabinoid receptors, to produce vasodilator effect in both intact‐endothelium and no‐endothelium rings, this effect was partially reverted when antagonist were used. Furthermore, involvement of big‐conductance voltage and calcium‐activated potassium (BKCa2+) channels was demonstrated by blocking with iberiotoxin. Moreover, using confocal microscopy we observed the cannabinoid receptors expression in transversal cuts, and the co‐localization of CB1 receptors and BKCa2+ channels was proved in dispersed smooth muscle cells. Therefore, cannabinoids elicit a vasodilator effect, through a mechanism dependent of the BKCa2+ channels activation.