1.An adrenomedullin fragment retains the systemic vasodepressor activity of rat adrenomedullin.
Lin B1, Gao Y, Chang JK, Heaton J, Hyman A, Lippton H. Eur J Pharmacol. 1994 Jul 21;260(1):1-4.
The present study was undertaken to investigate the effects of human adrenomedullin, a newly discovered peptide present in normal human plasma, as well as a fragment of adrenomedullin, on systemic hemodynamics in the anesthetized rat. Intravenous (i.v.) bolus injections of rat adrenomedullin, rat adrenomedullin-(11-50), human adrenomedullin-(13-52) decreased mean systemic arterial pressure in a dose-dependent manner. Since rat adrenomedullin and human adrenomedullin did not decrease cardiac output, the decreases in systemic arterial pressure reflect dose-dependent reductions in systemic vascular resistance. The systemic vasodepressor responses to similar doses of the adrenomedullin fragments studied and to their respective parent adrenomedullin peptides were similar. The present data demonstrate that the entire adrenomedullin molecule is not required for full systemic vasodilator activity in vivo suggesting that rat adrenomedullin-(11-50) or a structurally similar peptide, if formed endogenously, could mediate the hemodynamic properties of adrenomedullin in vivo.
2.Effects of calcitonin gene-related peptide receptor antagonists on renal actions of adrenomedullin.
Elhawary AM1, Poon J, Pang CC. Br J Pharmacol. 1995 Aug;115(7):1133-40.
1. Adrenomedullin is a novel vasoactive peptide which is produced in the lungs, ventricle, kidneys, heart and adrenal medulla. Adrenomedullin shows homology to calcitonin gene-related peptide (CGRP) and has similar pharmacological actions to CGRP. 2. This study examined the dose-response effects of adrenomedullin (rat, 11-50) on mean arterial pressure (MAP), heart rate (HR), renal blood flow (RBF), glomerular filtration rate (GFR) and renal tubular electrolyte excretion in Inactin-anaesthetized Sprague Dawley rats. The possible involvement of CGRP receptors in actions of adrenomedullin was also examined via renal arterial injection of a CGRP receptor antagonist, CGRP (8-37) (1 or 10 nmol kg-1) or [Tyr0]CGRP(28-37) (3 or 30 nmol kg-1), starting 15 min prior to the administration of adrenomedullin. 3. Renal arterial infusion (0.001 to 1 nmol kg-1) of adrenomedullin did not alter MAP, HR and renal K+ excretion but dose-dependently increased RBF and arterial conductance, GFR, urine flow and Na+ excretion.
3.Rat adrenomedullin induces a selective arterial vasodilation via CGRP1 receptors in the double-perfused mesenteric bed of the rat.
Berthiaume N1, Claing A, Lippton H, Cadieux A, D'Orléans-Juste P. Can J Physiol Pharmacol. 1995 Jul;73(7):1080-3.
The present work was undertaken to study the effect of rat adrenomedullin (rADM (1-50) and its C-terminal fragment (11-50)) in the endothelium-intact arterial and venous vasculatures of the rat perfused mesenteric bed. rADM (1-50) and the fragment rADM (11-50)(1-1000 pmol) induced a dose-dependent and endothelium-independent vasodilation on the arterial mesenteric vasculature. However, both peptides were inactive on the venous side of this vascular bed. The CGRP1 receptor antagonist, hCGRP8-37 (1 microM), markedly reduced the vasodilation caused by rADM (1-50) in the arterial mesenteric vasculature. Thus, our results show that rADM (1-50) in the arterial mesenteric vasculature. Thus, our results show that rADM (1-50) and its C-terminal fragment rADM(11-50) share properties similar to those of hCGRP. The blocking effect of hCGRP8-37 supports a role for CGRP1 receptor activation by adrenomedullin in this vascular preparation.
