The endogenous mu-opioid receptor agonists endomorphins 1 and 2 have novel hypotensive activity in the rabbit.

The endogenous peptides endomorphins 1 and 2 are newly isolated, potent, and selective mu-opioid receptor agonists. In the present study, responses to the endomorphin peptides were investigated in the systemic vascular bed of the rabbit. Endomorphins 1 and 2 induced dose-related decreases in systemic arterial pressure when injected in doses of 1-30 nmol/kg i.v. In terms of relative vasodepressor activity, endomorphins 1 and 2 were similar to the ORL1 receptor ligand, nociceptin (Orphanin FQ), and met-enkephalin in decreasing systemic arterial pressure. Vasodepressor responses to endomorphins 1 and 2 were inhibited by the opioid receptor antagonist, naloxone, in a dose of 2 mg/kg i.v. These results demonstrate that endomorphins 1 and 2 have significant naloxone-sensitive, vasodepressor activity in the rabbit.