Cannabinoids inhibit pre- and postjunctionally sympathetic neurotransmission in rat mesenteric arteries

The effects of cannabinoids on sympathetic neurotransmission in the rat isolated perfused mesenteric arterial bed, were investigated. Electrically evoked sympathetic neurogenic vasocontraction was inhibited by the cannabinoid receptor agonists 11-hydroxy-dimethylheptyl-Delta(8)-tetrahydrocannabinol (HU210), (-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]trans-4-(3-hydroxypropyl)-cyclohexanol (CP55,940) and methanandamide, and by (+)-11-hydroxy-Delta(8)-tetrahydrocannabinol (HU211), a (+)-stereoisomer of HU210. The inhibition was unaffected by cannabinoid CB(1) and CB(2) receptor antagonists. Electrically evoked release of endogenous noradrenaline from sympathetic nerves was inhibited by HU210, but not by HU211. Inhibition was blocked by a cannabinoid CB(1), but not a CB(2), receptor antagonist. HU210 attenuated contractions to noradrenaline, and all of the cannabinoids blocked contractions to KCl. Capsaicin pre-treatment had no significant effect on HU210- and CP55,940-mediated inhibition of sympathetic neurogenic contraction, but partly blocked inhibition mediated by methanandamide. These data show that cannabinoids can inhibit, by distinct pre- and postjunctional actions, sympathetic neurotransmission in the rat mesenteric arterial bed. The pre-junctional action is mediated by a cannabinoid CB(1)-like receptor, but the postjunctional action does not appear to involve either cannabinoid CB(1) or CB(2) receptors.