ACPA and JWH-133 modulate the vascular tone of superior mesenteric arteries through cannabinoid receptors, BKCa channels, and nitric oxide dependent mechanisms.

Abstract Background Some cannabinoids, a family of compounds derived from Cannabis sativa (marijuana), have previously shown vasodilator effects in several studies, a feature that makes them suitable for the generation of a potential treatment for hypertension. The mechanism underlying this vasodilator effect in arteries is still controversial. In this report, we explored how the synthetic cannabinoids ACPA (CB 1 -selective agonist) and JWH-133 (CB 2 -selective agonist) regulate the vascular tone of rat superior mesenteric arteries. Methods To screen the expression of CB 1 (Cannabinoid receptor 1) and CB 2 (Cannabinoid receptor 2) receptors in arterial rings or isolated smooth muscle cells obtained from the artery, immunocytochemistry, immunohistochemistry, and confocal microscopy were performed. In addition, the effects on vascular tone induced by the two cannabinoids were tested in isometric tension experiments in rings obtained from superior mesenteric arteries. The participation of voltage and calcium-activated potassium channel of big conductance (BK Ca ) and the role of nitric oxide (NO) release on the vascular effects induced by ACPA and JWH-133 were tested. Results CB 1 and CB 2 receptors were highly expressed in the rat superior mesenteric artery, in both smooth muscle and endothelium. The vasodilation effect shown by ACPA was endothelium-dependent through a mechanism involving CB 1 receptors, BK Ca channel activation, and NO release; meanwhile, the vasodilator effect of JWH-133 was induced by the activation of CB 2 receptors located in smooth muscle and by a CB 2 receptor-independent mechanism inducing NO release. Conclusions CB 1 and CB 2 receptor activation in superior mesenteric artery causes vasorelaxation by mechanisms involving BK Ca channels and NO release.