Capsaicin Causes Vasorelaxation of Rat Aorta through Blocking of L-type Ca2+ Channels and Activation of CB1 Receptors.

Felipa Andrade,Evelyn López-Dyck,Alejandro Elizalde,Adolfo Virgen-Ortiz,Edgar Bonales-Alatorre,Alejandrina Rodríguez-Hernández,Enrique Sánchez-Pastor,Georgina Valencia-Cruz,Cinthia Rangel-Sandoval

doi:10.3390/molecules25173957

Abstract

The aim of this work was to determine whether Capsaicin may exert a vascular regulation through the activation of CB1 and/or CB2 receptors causing vasorelaxation in the rat aorta. Our results show the location of TRPV1 mainly in the endothelial and smooth muscle cells membrane. Nevertheless, Capsaicin caused vasorelaxation of this artery through a mechanism independent of TRPV1, since the specific antagonists Capsazepine and SB-366791 did not block the effect of Capsaicin. Because the significant expression of CB1 and CB2 receptors has been previously reported in the rat aorta, we used antagonists for these two receptors prior to the addition of Capsaicin. In these experiments, we found that the inhibition of CB1 using AM281, decreases the vasorelaxant effect caused by Capsaicin. On the other hand, the vasorelaxant effect is not altered in the presence of the CB2 receptor antagonist AM630. Furthermore, a partial decrease of the effect of Capsaicin was also seen when L-type calcium channels are blocked. A complete block of Capsaicin-induced vasorelaxation was achieved using a combination of Verapamil and AM281. In accordance to our results, Capsaicin-induced vasorelaxation of the rat aorta is neither dependent of TRPV1 or CB2 receptors, but rather it is strongly suggested that a tandem mechanism between inactivation of L-type calcium channels and the direct activation of CB1 receptors is involved. These findings are supported by CB1 docking simulation which predicted a binding site on CB1 receptors for Capsaicin.

Highlights

Blood pressure mainly depends on vascular tone, which is regulated by several mechanisms.These mechanisms include the release of some substances from the inner lining of the arteries such as NO, which causes dilation of the arteries or endothelin, which causes vasoconstriction [1]
Indicates a significant conditions. * indicates a significant change in tension compared to Phe pre-contraction. **change indicates a compared to thechange effect of significant compared the effect of Capsaicin alone
In order to determine the role of TRPV1 receptors in the vasorelaxant effect caused by Capsaicin, 30 min before Phe pre-contracture, the rings were incubated with the antagonist Capsazepine

Summary

Introduction

Blood pressure mainly depends on vascular tone, which is regulated by several mechanisms.These mechanisms include the release of some substances from the inner lining of the arteries such as NO, which causes dilation of the arteries or endothelin, which causes vasoconstriction [1]. TRPV1 is expressed in the smooth muscle and endothelium of the aorta and in some other arteries, this receptor may have a very important role in the regulation of vascular tone [3]. These receptors can be activated by ligands such as capsaicinoids—one of these compounds is capsaicin (a component of hot peppers)—by endogenous ligands such as the endocannabinoid anandamide, and by other factors such as acidic pH (43 ◦ C) [2]

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