Characterization of hypotensive and vasorelaxant effects of PHAR-DBH-Me a new cannabinoid receptor agonist.

Abstract

The effect of PHAR-DBH-Me, a cannabinoid receptor agonist, on different cardiovascular responses in adult male rats was analyzed. The blood pressure was measured directly and indirectly. The coronary flow was measured by Langendorff preparation, and vasomotor responses induced by PHAR-DBH-Me in aortic rings pre-contracted with phenylephrine (PHEN) were analyzed. The intravenous injection of the compound PHAR-DBH-Me (0.018–185 µg/kg) resulted in decreased blood pressure; maximum effect was observed at the dose of 1,850 µg/kg. A concentration-dependent increase in the coronary flow was observed in a Langendorff preparation. In the aortic rings, with and without endothelium, pre-contracted with PHEN (10–6 M), the addition of PHAR-DBH-Me to the superfusion solution (10–12–10–5 M), produced a vasodilator response, which depends on the concentration and presence of the endothelium. L-NAME inhibited these effects. Addition of CB1 receptor antagonist (AM 251) did not modify the response, while CB2 receptor antagonist (AM630) decreased the potency of relaxation elicited by PHAR-DBH-Me. Indomethacin shifted the curve concentration-response to the left and produced an increase in the magnitude of the maximum endothelium dependent response to this compound. The maximum effect of PHAR-DBH-Me was observed with the concentration of 10–5 M. These results show that PHAR-DBH-Me has a concentration-dependent and endothelium-dependent vasodilator effect through CB2 receptor. This vasodilation is probably mediated by the synthesis/release of NO. On the other hand, it is suggested that PHAR-DBH-Me also induces the release of a vasoconstrictor prostanoid.