Vasodilation and glomerular binding of adrenomedullin in rabbit kidney are not CGRP receptor mediated.
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.
Hjelmqvist
H
H
Max-Planck Institute for Physiological and Clinical Research, W. G. Kerckhoff Institute, Bad Nauheim, Germany.
Keil
R
R
Mathai
M
M
Hübschle
T
T
Gerstberger
R
R
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
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