Comparison of responses to adrenomedullin and calcitonin gene-related peptide in the pulmonary vascular bed of the cat.
Pulmonary vascular responses to the newly discovered hypotensive peptide, adrenomedullin, were compared with responses to the structurally related peptides, calcitonin gene-related peptide (CGRP) and amylin, in the intact-chest cat. Under conditions of controlled blood flow, when tone in the pulmonary vascular bed had been raised to a high steady level, intralobar injections of adrenomedullin (0.03-1 nmol), CGRP (0.1-3 nmol), and amylin (0.1 and 0.3 nmol) caused dose-related decreases in lobar arterial pressure without changing left atrial pressure. In terms of relative vasodilator activity in the pulmonary vascular bed, the dose of the peptide that decreased lobar arterial pressure 7.5 mm Hg (ED7.5 mm Hg) was significantly lower for adrenomedullin than for CGRP. The duration of the pulmonary vasodilator responses to CGRP was longer than for adrenomedullin, and both peptides decreased systemic arterial pressure when injected into the perfused lobar artery in the higher doses studied. The present data demonstrate that synthetic human adrenomedullin and CGRP have potent but relatively short-lasting vasodilator activity in the pulmonary vascular bed. These data show also that amylin, a structurally related pancreatic peptide, also has significant pulmonary vasodilator activity.
DeWitt
B J
BJ
Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA 70112.
Cheng
D Y
DY
Caminiti
G N
GN
Nossaman
B D
BD
Coy
D H
DH
Murphy
W A
WA
Kadowitz
P J
PJ
D053607:Adrenomedullin; D000682:Amyloid / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D002415:Cats; D004305:Dose-Response Relationship, Drug; D005260:Female; D058228:Islet Amyloid Polypeptide; D008168:Lung / Q000098:blood supply; D008297:Male; D010455:Peptides / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000187:drug effects; D011667:Pulmonary Veins / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
D000682:Amyloid; D000959:Antihypertensive Agents; D058228:Islet Amyloid Polypeptide; D010455:Peptides; D053607:Adrenomedullin; D015740:Calcitonin Gene-Related Peptide