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

• Published in: Prostaglandins & other lipid mediators Vol. 134; pp. 77 - 83
• Main Authors: Szekeres, Mária, Nádasy, György L., Soltész-Katona, Eszter, Hunyady, László
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2018
• Subjects: Angiotensin II; Animals; Arterioles - drug effects; Arterioles - physiology; Cannabinoid; Cannabinoids - pharmacology; Coronary artery; Coronary Vessels - drug effects; Coronary Vessels - physiology; Diacylglycerol; Dose-Response Relationship, Drug; Endocannabinoids - metabolism; Gene Expression Regulation - drug effects; Lipoprotein Lipase - metabolism; Male; Rats; Rats, Wistar; Receptor, Cannabinoid, CB1 - agonists; Receptor, Cannabinoid, CB1 - metabolism; Vascular tone; Vasoconstriction - drug effects; NO; PLC; Diacylglycerol; BK; Cannabinoid; THC; SNP; THL; Angiotensin II; EC; HPLC; KO; Ach; qRT-PCR; Coronary artery; AT1R; DAG; Ang II; LAD; MAG; Vascular tone; 2-AG; VSMC; DAGL; LNA; CB1R; ERK
• ISSN: 1098-8823
• DOI: 10.1016/j.prostaglandins.2017.10.001

•Protein and mRNA of the Cannabinoid Receptor Type 1 are present in intramural coronary resistance arteries of the rat. Its exogenous stimulation induces substantial coronary vasodilation.•Endocannabinoid production in the wall (with all probability 2-arachidonoylglycerol, 2-AG) continuously reduces coronary resistance artery tone as it could be observed by pressure arteriography of isolated segments using receptor antagonists and inhibitor of synthesis.•Both characteristic for these vessels myogenic tone and agonist-induced tone are kept substantially moderated by this intrinsic coronary vasodilatory mechanism. 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.