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 now 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.