title: Vasodilation and glomerular binding of adrenomedullin in rabbit kidney are not CGRP receptor mediated.
abstract: The polypeptide adrenomedullin (ADM) was infused systemically to conscious rabbits to elucidate its actions on overall circulation and especially the renovascular bed and the formation and/or release of hormones important for body fluid homeostasis, including adrenocortical steroids. ADM lowered mean arterial pressure from 71.5 +/- 3.2 to 64.7 +/- 3.2 mmHg only at the highest dose of 25 pmol.min-1.kg-1 infused intravenously for 20 min and concomitantly induced tachycardia, possibly due to both baroreflex activation and direct cardiostimulatory effects. Renal blood flow (RBF) determined in rabbits chronically equipped with a perivascular ultrasonic flow probe increased from 55.4 +/- 2.1 to 67.4 +/- 2.7 and from 58.2 +/- 3.5 to 75.2 +/- 6.0 ml/min at ADM infusions of 5 and 25 pmol.min-1.kg-1, respectively. The elevation in RBF persisted even in the presence of the calcitonin gene-related peptide (CGRP1 receptor antagonist CGRP-(8-37). Of all osmoregulatory hormones tested, only corticosterone (Cort) plasma concentration increased in response to the highest ADM dose from 17.6 +/- 3.1 to 38.9 +/- 6.2 ng/ml, probably due to haroreflex activation. Subdepressor doses of ADM, however, caused a mild reduction in circulating Cort. Expression of functional high-affinity binding sites specific for ADM in vitro could be demonstrated for the renal artery and outer cortical glomeruli using 125I-labeled rat ADM as radioligand and determination of cellular adenosine 3',5'-cyclic monophosphate (cAMP) formation within the glomeruli. The ineffectiveness of CGRP-(8-37) to displace radiolabeled ADM from its binding sites, to inhibit ADM-induced glomerular cAMP formation, and to prevent ADM-induced renal vasodilation supports the hypothesis of ADM altering renal hemodynamics by interacting with ADM- and not CGRP-specific membrane receptors.
authors.affiliation: Max-Planck Institute for Physiological and Clinical Research, W. G. Kerckhoff Institute, Bad Nauheim, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Hjelmqvist
authors.forename: R
authors.initials: R
authors.lastname: Keil
authors.forename: M
authors.initials: M
authors.lastname: Mathai
authors.forename: T
authors.initials: T
authors.lastname: Hübschle
authors.forename: R
authors.initials: R
authors.lastname: Gerstberger
mesh_terms: D053607:Adrenomedullin; D000818:Animals; D001665:Binding Sites; D001833:Body Temperature Regulation / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects; D002682:Chinchilla; D000242:Cyclic AMP / Q000096:biosynthesis; D005260:Female; D006728:Hormones / Q000097:blood; D007668:Kidney / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D010455:Peptides / Q000378:metabolism* / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000502:physiology*; D012077:Renal Artery / Q000378:metabolism; D014664:Vasodilation / Q000502:physiology*; D014665:Vasodilator Agents / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D006728:Hormones; D010446:Peptide Fragments; D010455:Peptides; D018015:Receptors, Calcitonin Gene-Related Peptide; D014665:Vasodilator Agents; C108043:adrenomedullin (1-50); D053607:Adrenomedullin; D000242:Cyclic AMP