Eduardo Rivera- Mancilla (Rotterdam/ NL), Antoon van den Bogaerdt (Beverwijk/ NL), A.H. Jan Danser (Rotterdam/ NL), Carlos M. Villalón (Mexico City/ MX), Antoinette Maassen van den Brink (Rotterdam/ NL)
Abstract text (incl. figure legends and references)
Background: The use of cannabis and its derivatives has increased during the last years due to their therapeutic potential. However, the exact mechanisms of action of cannabinoids are still limited. It has been suggested that cannabinoids can exert their effects via the activation of cannabinoid receptors (i.e. CB1 or CB2 receptors) and/or transient receptor potential vanilloid 1 (TRPV1) channels, suggesting an interaction between both systems. We investigated the role of CB receptors in the vasodilatory effects induced by capsaicin in human isolated coronary arteries (HCAs).
Methods: In HCAs (female, n=5; 56±5 years and male, n=4; 57±4 years), the vasodilatory responses to capsaicin (TRPV1 channel agonist) were evaluated in the absence or presence of the antagonists capsazepine (TRPV1, 5 µM); AM6545 (CB1 receptor, 1 µM); AM630 (CB2 receptor, 1 µM); O-1918 (putative endothelial CB receptor, 10 µM) or cannabidiol (GPR55 receptor, 1 µM) to obtain the maximum contractile response (Emax).
Results: Capsaicin induced concentration-dependent relaxation responses (Emax 109±8%), which were significantly reduced by AM6545 (Emax 87±4%) or cannabidiol (Emax 86±3%), but not by capsazepine (Emax 103±6%), AM630 (Emax 100±3%) or O-1918 (Emax 93±5%). Moreover, pilot experiments (n=2) showed that the maximal response induced by N-arachidonoylethanolamine, (ACEA, a CB1 receptor agonist; Emax 43±7%) is inhibited by AM6545 or capsazepine: Emax 16±3% and 21±4%, respectively.
Conclusions: (i) Capsaicin-induced relaxation responses are mediated by CB1 and GRP55 receptors; and (ii) TRPV1 channels may be involved in the modulation of the ACEA-induced relaxation responses. Thus, we can suggest that the CB and vanilloid systems may share a signaling pathway to modulate the vascular tone, which may provide novel therapeutic targets for vascular disorders (e.g. migraine and its related cardiovascular events). Further studies should elucidate additional mechanisms involved in these responses.