Adrenomedullin (16-31) has pressor activity in the rat but not the cat.
Responses to a newly synthesized human adrenomedullin (hADM) analog, hADM (16-31), were investigated in the rat and cat. Unlike the full-sequence peptide, which has potent hypotensive activity, hADM (16-31) had pressor activity in the rat but not in the cat. Injection of hADM (16-31) in doses of 10-300 nmol/kg i.v. induced dose-dependent increases in systemic arterial pressure in the rat, and the peptide was approximately 10-fold less potent than norepinephrine when doses are compared on a nanomole basis. In contrast, injection of hADM (16-31) in doses up to 1,000 nmol/kg i.v. had no significant effect on systemic arterial pressure in the cat. Increases in systemic arterial pressure in response to hADM (16-31) in the rat were significantly reduced after administration of phentolamine or reserpine. These data suggest that increases in systemic arterial pressure in response to hADM (16-31) are mediated by release of catecholamines and activation of alpha-adrenergic receptors in the rat. These data show that hADM (16-31) has significant pressor activity and that there are marked species differences in the response to hADM (16-31).
Champion
H C
HC
Department of Pharmacology, Tulane University, School of Medicine, New Orleans, LA 70112, USA.
Friedman
D E
DE
Lambert
D G
DG
Murphy
W A
WA
Coy
D H
DH
Kadowitz
P J
PJ
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D053607:Adrenomedullin; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002415:Cats; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*; D010646:Phentolamine / Q000494:pharmacology; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000502:physiology; D012110:Reserpine / Q000494:pharmacology; D014439:Tyramine / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D018759:Adrenergic Uptake Inhibitors; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D010446:Peptide Fragments; D010455:Peptides; D011942:Receptors, Adrenergic, alpha; D014662:Vasoconstrictor Agents; C107471:adrenomedullin(16-31); D053607:Adrenomedullin; D012110:Reserpine; D009638:Norepinephrine; D014439:Tyramine; D010646:Phentolamine