Pulmonary vasorelaxant activity of atrial peptides.
Pulmonary vascular relaxant effects of the 28-amino acid atrial natriuretic peptide and atriopeptins I, II and III (21, 23 and 24 amino acid peptides, respectively) were studied in isolated blood vessels and in perfused rat lungs. In isolated tissue studies, intrapulmonary arteries were more responsive to the relaxant effects of atrial peptides than the main pulmonary artery or aorta. In perfused lung preparations, each of the four atrial peptides produced dose-dependent pulmonary vasodilation of PGF2 alpha or hypoxia-induced pulmonary vasoconstriction. Atriopeptin I was the least potent pulmonary vasodilator peptide in all studies. Pretreatment of perfused lungs with various peptidase inhibitors, including the angiotensin converting enzyme inhibitors, captopril and MK-521, the carboxypeptidase inhibitor, 1,10-phenanthroline, and the aminopeptidase inhibitor, bestatin, variably potentiated the pulmonary vasodilator activities of the atrial peptides. The results demonstrate that atrial peptides released from the right heart into the pulmonary circulation can have potent vasorelaxant effects in the pulmonary vascular bed and further suggest that upon passage through the lung atrial peptides may undergo metabolic degradation that alters their pulmonary vasodilator activities.
Numan
N A
NA
University of Kentucky, College of Pharmacy, Lexington.
Gillespie
M N
MN
Altiere
R J
RJ
D000626:Aminopeptidases / Q000037:antagonists & inhibitors; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D002268:Carboxypeptidases / Q000037:antagonists & inhibitors; D004347:Drug Interactions; D004656:Enalapril / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D017706:Lisinopril; D008297:Male; D010477:Perfusion; D010618:Phenanthrolines / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D014665:Vasodilator Agents / Q000494:pharmacology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D010618:Phenanthrolines; D014665:Vasodilator Agents; D004656:Enalapril; D009320:Atrial Natriuretic Factor; D017706:Lisinopril; D002268:Carboxypeptidases; D000626:Aminopeptidases; D007930:Leucine; C012211:ubenimex; C025205:1,10-phenanthroline