Comparison of responses to adrenomedullin and adrenomedullin analogs in the mesenteric vascular bed of the cat.
Responses to adrenomedullin, a newly discovered hypotensive peptide isolated from human pheochromocytoma cells, and the carboxy terminal 15-52 (adrenomedullin-(15-52)) and 22-52 (adrenomedullin-(22-52)) amino acid fragments of adrenomedullin were investigated in the mesenteric vascular bed of the cat. Under constant flow conditions, injections of adrenomedullin, adrenomedullin-(15-52), and calcitonin gene-related peptide (CGRP) in doses of 0.003-1 nmol into the perfused superior mesenteric artery caused significant dose-related decreases in mesenteric arterial perfusion pressure. Mesenteric vasodilator responses to adrenomedullin and adrenomedullin-(15-52) were similar in magnitude and duration, while vasodilator responses to CGRP were greater in magnitude and longer in duration than those produced by adrenomedullin or adrenomedullin-(15-52) when these agents were injected in doses of 0.1-1 nmol. Adrenomedullin-(22-52) caused no significant change in mesenteric arterial perfusion pressure when injected in doses up to 10 nmol. These results suggest that amino acids 15-52 and the six-membered ring structure of adrenomedullin are important for the expression of vasodilator activity in the mesenteric vascular bed of the cat.
Santiago
J A
JA
Department of Pharmacology and Medicine, Tulane University School of Medicine, New Orleans, LA 70112.
Garrison
E
E
Purnell
W L
WL
Smith
R E
RE
Champion
H C
HC
Coy
D H
DH
Murphy
W A
WA
Kadowitz
P J
PJ
D053607:Adrenomedullin; D000595:Amino Acid Sequence; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D015740:Calcitonin Gene-Related Peptide / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D002415:Cats; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D007269:Injections, Intra-Arterial; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000378:metabolism; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D010455:Peptides / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D011994:Recombinant Proteins; D013329:Structure-Activity Relationship; D014664:Vasodilation / Q000187:drug effects
D000959:Antihypertensive Agents; D010446:Peptide Fragments; D010455:Peptides; D011994:Recombinant Proteins; D053607:Adrenomedullin; D015740:Calcitonin Gene-Related Peptide