Synthetic human adrenomedullin and adrenomedullin 15-52 have potent short-lived vasodilator activity in the hindlimb vascular bed of the cat.
Responses to synthetic human adrenomedullin, a novel hypotensive peptide isolated from human pheochromocytoma cells, and the carboxy terminal 15-52 amino acid fragment of adrenomedullin (ADM15-52) were investigated in the hindlimb vascular bed of the cat under constant flow conditions. Intraarterial injections of the peptides in doses of 0.01-0.3 nmol caused dose-related decreases in hindlimb perfusion pressure. When compared on a nmol basis, adrenomedullin and ADM15-52 were similar to bradykinin in vasodilator potency and were approximately 10 fold less potent than acetylcholine. The half-life of the vasodilator response to adrenomedullin and ADM15-52 ranged from 55 to 80 sec and was greater than the half-life of vasodilator responses to bradykinin in doses of 0.01-0.3 nmol and acetylcholine in doses of 0.01-0.3 nmol. The present data demonstrate that synthetic human adrenomedullin and ADM15-52 have potent but relatively short-lasting vasodilator activity in the hindlimb vascular bed of the cat. These data suggest that amino acid residues 15-52 of adrenomedullin are important for the expression of vasodilator activity in the hindlimb vascular bed of the cat.
Santiago
J A
JA
Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA 70112.
Garrison
E A
EA
Ventura
V L
VL
Coy
D H
DH
Bitar
K
K
Murphy
W A
WA
McNamara
D B
DB
Kadowitz
P J
PJ
D053607:Adrenomedullin; D000818:Animals; D002415:Cats; D004305:Dose-Response Relationship, Drug; D005260:Female; D006614:Hindlimb / Q000098:blood supply; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
D010446:Peptide Fragments; D010455:Peptides; D014665:Vasodilator Agents; D053607:Adrenomedullin