Anandamide Induces Endothelium-Dependent Vasoconstriction and CGRPergic Nerve–Mediated Vasodilatation in the Rat Mesenteric Vascular Bed

Abstract

An endogenous cannabinoid anandamide (N-arachidonoylethanolamide) has been shown to cause vasodilatation in vitro and a brief vasoconstriction followed by prolonged depressor response in vivo. This study investigated the vascular effects of anandamide and underlying mechanisms in rat mesenteric vascular beds. In preparations with an intact endothelium and active tone, anandamide at low concentrations (0.1 - 1 nM) caused a concentration-dependent decrease in perfusion pressure due to vasodilatation, but at high concentrations (10 nM - 1 µM) elicited an initial and sharp increase in perfusion pressure due to vasoconstriction followed by long-lasting vasodilatation in a concentration-dependent manner. Treatment with SR141716A [cannabinoid-1 (CB(1))-receptor antagonist] blunted both the vasoconstrictor and vasodilator responses. Also, removal of the endothelium and indomethacin (cyclooxygenase inhibitor), but not adrenergic denervation with 6-hydoxydopamine (adrenergic neurotoxin), markedly inhibited the vasoconstrictor response to anandamide, while these treatments did not affect vasodilatation. The vasodilatation, but not vasoconstriction, in response to anandamide was markedly attenuated by capsazepine [selective antagonist for transient receptor potential vanilloid-1 (TRPV1)], pretreatment with capsaicin [calcitonin gene-related peptide (CGRP)ergic-nerve depletor], or cold-storage denervation. These results suggest that in rat mesenteric vascular beds, anandamide causes CB(1)-receptor- and prostanoid-mediated endothelium-dependent vasoconstriction and perivascular capsaicin-sensitive CGRPergic nerve-mediated vasodilatation.

Effects of capsaicin application on the skin during resting exposure to temperate and warm conditions

“…Moreover, the activation of TRPV1 channels may induce vasodilation via increased release of calcitonin gene-related peptide (CGRP). 33 In support of this, recent findings indicate that the activation of TRPV1 channels through capsaicin ingestion modulate vascular function by opposing a-adrenergic receptor-mediated vasoconstriction and potentiating vasorelaxation. 34 Hence, the observed lower total peripheral resistance is possibly linked with the capsaicin-induced vasorelaxation or with NO increase and/or CGRP release.…”

“…Noteworthily, Yang et al observed that TRPV1 activation by capsaicin enhanced endothelium‐dependent vasorelaxation and that this effect was absent in TRPV1 deficient mice. Moreover, the activation of TRPV1 channels may induce vasodilation via increased release of calcitonin gene‐related peptide (CGRP) . In support of this, recent findings indicate that the activation of TRPV1 channels through capsaicin ingestion modulate vascular function by opposing a‐adrenergic receptor‐mediated vasoconstriction and potentiating vasorelaxation .…”

Mechanisms of endothelium-dependent relaxation evoked by anandamide in isolated human pulmonary arteries

“…CB 1 receptors are not involved in the AEA-mediated vasorelaxation since the respective receptor antagonist AM251 (1 μM; Wheal et al 2010) did not influence the CRC of anandamide. The involvement of CB 2 and vanilloid TRPV1 receptors could also be excluded since the respective antagonists at these receptors, SR144528 (1 μM; Kozłowska et al 2008) and capsazepine (1 μM; Tamaki et al 2012), failed to modify the vasorelaxant effect of anandamide. By contrast, O-1918 (10 μM; pA 2  = 6.3 and 6.0; Kozłowska et al 2008; Baranowska-Kuczko et al 2012, respectively) shifted to the right of the CRC for anandamide, suggesting that this receptor plays a role in the anandamide-induced vasorelaxation.…”

Involvement of the TRPV1 channel in the modulation of spontaneous locomotor activity, physical performance and physical exercise-induced physiological responses

“…Moreover, dietary capsaicin enhances TRPV1 expression in endothelial cells, and this response is associated with an increase in endothelium-dependent vasodilation ( 68 ). The activation of the TRPV1 channels also induces vasodilation via increased release of the calcitonin gene-related peptide at the nerve terminals of capsaicin-sensitive neurons that innervate peripheral arteries ( 70 ). This vasodilation seems to mediate the decrease in blood pressure observed after the administration of TRPV1 agonists.…”