Vasodilation and glomerular binding of adrenomedullin in rabbit kidney are not CGRP receptor mediated
Hjelmqvist, H.; Keil, R.; Mathai, M.; Hübschle, T.; Gerstberger, R.
American Journal of Physiology 273(2 Pt 2): R716-R724
1997
ISSN/ISBN: 0002-9513 PMID: 9277560 Document Number: 482455
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 cntdot min-1 cntdot 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 cntdot min-1 cntdot kg-1, respectively. The elevation in RBF persisted even in the presence of the calcitonin gene-related peptide (CGRP) 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 baroreflex 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.