Capsaicin Causes Vasorelaxation of Rat Aorta by Activation of CB1 Receptors but not by Trpv1 or CB2 Receptors

Abstract

Blood pressure mainly depends on vascular tone, which is regulated by several mechanisms. Some substances like cannabinoids cause vasorelaxation not only by interacting on cannabinoid receptors (CB1 or CB2) but also by interacting with some other receptors (TRPV1, GPR55) or with ion channels. The main TRPV1 agonist (capsaicin) can cause vasorelaxation in several artery preparations as well. However, there is still lack of evidence to know the mechanism of action of capsaicin in modulating the vascular tone. Although there are some reports implicating the role of TRPV1 in the modulation of vascular tone, in our Lab and in a recent report, it was found that capsaicin caused vasorelaxation of rat aorta by a mechanism independent of TRPV1. Thus, the aim of this work was to determine the possible role of CB1 and CB2 receptors on the vasorelaxation caused by capsaicin in rat aorta. Our results show, by confocal microscopy, the localization of TRPV1 on endothelial and smooth muscle cells of rat aorta. However, capsaicin caused vasorelaxation of this artery through a mechanism independent of TRPV1, since the antagonist capsazepine did not block the effect of capsaicin. Moreover, as the expression of CB1 and CB2 receptors has been reported in aorta, we used antagonists for these receptors prior to the evaluation of capsaicin. In these experiments we found that using the CB1 antagonist AM281 partially blocked the vasorelaxant effect observed with capsaicin alone. On the other hand, by incubating with the CB2 antagonist AM630, we found that capsaicin caused a vasorelaxation similar to control conditions. Thereby, our results show that the vasorelaxant effect of capsaicin on rat aorta did not depend on TRPV1 or CB2 receptors, but partially depends on CB1 activation.