ENDOMORPHIN-1 AND ENDOMORPHIN-2, ENDOGENOUS LIGANDS FOR THE MU-OPIOIDRECEPTOR, DECREASE CARDIAC-OUTPUT, AND TOTAL PERIPHERAL RESISTANCE INTHE RAT

Endomorphin 1 and 2 are recently discovered endogenous ligands for the mu-opioid receptor. In the present study, responses to intravenous ad ministration of endomorphin 1 and 2 were investigated in the systemic vascular bed of the rat. Endomorphin 1 and 2 induced dose-related decr eases in systemic arterial pressure when injected in doses of 10-100 n mol/kg IV. The decreases in systemic arterial pressure in response to endomorphin 1 and 2 were associated with significant decreases in hear t rare, cardiac output, and total peripheral resistance. The endogenou s ligand for the ORL1 receptor, nociceptin/OFQ had similar effects on systemic arterial pressure, heart rate, cardiac output, and total peri pheral resistance in the rat. Injections of isoproterenol (1 mu g/kg I V) and calcitonin gene-related peptide (CGRP; 0.3 nmol/kg IV), decreas ed systemic arterial pressure and total peripheral resistance. However these decreases in arterial pressure were associated with increases i n heart rate and cardiac output. The results of the present study demo nstrate that the endomorphin peptides have significant vasodilator act ivity in the systemic vascular bed of the rat and show that this respo nse is associated with a decrease in heart rate and cardiac output. (C ) 1997 Elsevier Science Inc.