Synthetic human adrenomedullin and adrenomedullin 15-52 have potent short-lived vasodilator activity in the hindlimb vascular bed of the cat |
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Institution: | 1. University of California, Los Angeles, United States;2. Veterans Affairs Puget Sound Health Care System, United States;1. Department of Energy Science and Engineering, Indian Institute of Technology Bombay, 400076, India;2. Rural Electrification Corporation Limited (REC), New Delhi, 110003, India;3. Department of Built Environment and Energy Technology, Linnaeus University, 351 95 Växjö, Sweden |
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Abstract: | Responses to synthetic human adrenomedullin, a novel hypotensive peptide isolated from human pheochromccytoma 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 visodilator 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. |
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