title: Endomorphin 1 and 2, endogenous ligands for the mu-opioid receptor, decrease cardiac output, and total peripheral resistance in the rat.
abstract: Endomorphin 1 and 2 are recently discovered endogenous ligands for the mu-opioid receptor. In the present study, responses to intravenous administration of endomorphin 1 and 2 were investigated in the systemic vascular bed of the rat. Endomorphin 1 and 2 induced dose-related decreases in systemic arterial pressure when injected in doses of 10-100 nmol/kg i.v.. The decreases in systemic arterial pressure in response to endomorphin 1 and 2 were associated with significant decreases in heart rate, cardiac output, and total peripheral resistance. The endogenous ligand for the ORL1 receptor, nociceptin/OFQ had similar effects on systemic arterial pressure, heart rate, cardiac output, and total peripheral resistance in the rat. Injections of isoproterenol (1 microgram/kg i.v.) and calcitonin gene-related peptide (CGRP; 0.3 nmol/kg i.v.), decreased systemic arterial pressure and total peripheral resistance. However these decreases in arterial pressure were associated with increases in heart rate and cardiac output. The results of the present study demonstrate that the endomorphin peptides have significant vasodilator activity in the systemic vascular bed of the rat and show that this response is associated with a decrease in heart rate and cardiac output.
authors.affiliation: Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA. champion@mailhost.tcs.tulane.edu
authors.forename: H C
authors.initials: HC
authors.lastname: Champion
authors.forename: J E
authors.initials: JE
authors.lastname: Zadina
authors.forename: A J
authors.initials: AJ
authors.lastname: Kastin
authors.forename: L
authors.initials: L
authors.lastname: Hackler
authors.forename: L J
authors.initials: LJ
authors.lastname: Ge
authors.forename: P J
authors.initials: PJ
authors.lastname: Kadowitz
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D002302:Cardiac Output / Q000187:drug effects*; D002316:Cardiotonic Agents / Q000494:pharmacology; D005260:Female; D007545:Isoproterenol / Q000494:pharmacology; D008024:Ligands; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology*; D018847:Opioid Peptides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000819:agonists*; D014655:Vascular Resistance / Q000187:drug effects*; D000097629:Nociceptin
chemical_list: D015740:Calcitonin Gene-Related Peptide; D002316:Cardiotonic Agents; D007545:Isoproterenol; D008024:Ligands; D009842:Oligopeptides; D018847:Opioid Peptides; D017450:Receptors, Opioid, mu; D000097629:Nociceptin; C105293:endomorphin 1; C105294:endomorphin 2