Control of myogenic tone and agonist induced contraction of intramural coronary resistance arterioles by cannabinoid type 1 receptors and endocannabinoids

Publication date: Available online 16 October 2017 Source:Prostaglandins & Other Lipid Mediators Author(s): Mária Szekeres, György L. Nádasy, Eszter Soltész-Katona, László Hunyady It was tested whether intrinsic CB1R activation modifies myogenic and agonist induced contraction of intramural coronary resistance arteries of the rat. CB1R protein was detected by immuno-histochemistry and by Western blot, its mRNA by qRT-PCR in their wall. Microsurgically prepared cylindrical coronary segments (∼100–150μm) developed myogenic contraction (∼20% of relaxed luminal diameter), from which a substantial relaxation (∼15%) in response to WIN55212 (a specific agonist of the CB1Rs) has been found. CB1R-mediated relaxation was blocked by O2050 and AM251 (neutral antagonist and inverse agonist of the CB1R, respectively) and was partially blocked by the NO synthase blocker Nω-nitro-L-arginine. CB1R blockade enhanced myogenic tone and augmented AngII-induced vasoconstriction (from 17.8±1.2 to 29.1±2.9%, p<0.05). Inhibition of diacylglycerol lipase by tetrahydrolipstatin, (inhibitor of endogenous 2-AG production) also augmented coronary vasoconstriction. These observations prove that vascular endocannabinoids are significant negative modulators of the myogenic and agonist-induced tone of intramural coronary arterioles acting through CB1Rs.

Source: Prostaglandins and Other Lipid Mediators - November 19, 2017 Category: Lipidology Source Type: research