VASODILATION AND GLOMERULAR BINDING OF ADRENOMEDULLIN IN RABBIT KIDNEY ARE NOT CGRP RECEPTOR-MEDIATED

The polypeptide adrenomedullin (ADM) was infused systemically to consc ious rabbits to elucidate its actions on overall circulation and espec ially the renovascular bed and the formation and/or release of hormone s important for body fluid homeostasis, including adrenocortical stero ids. 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 in travenously for 20 min and concomitantly induced tachycardia, possibly due to both baroreflex activation and direct cardiostimulatory effect s. Renal blood flow (RBF) determined in rabbits chronically equipped w ith a perivascular ultrasonic flow probe increased from 55.4 +/- 2.1 t o 67.4 +/- 2.7 and from 58.2 +/- 3.5 to 75.2 +/- 6.0 ml/min at ADM inf usions of 5 and 25 pmol.min-1.kg(-1), respectively. The elevation in R BF persisted even in the presence of the calcitonin gene-related pepti de (CORP) receptor antagonist CGRP-(8-37), Of all osmoregulatory hormo nes 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 AD M, however, caused a mild reduction in circulating Cort. Expression of functional high-affinity binding sites specific for ADM in vitro coul d be demonstrated for the renal artery and outer cortical glomeruli us ing I-125-labeled rat ADM as radioligand and determination of cellular adenosine 3',5'-cyclic monophosphate (cAMP) formation within the glom eruli. The ineffectiveness of CGRP-(8-37) to displace radiolabeled ADM from its binding sites, to inhibit ADM-induced glomerular cAMP format ion, and to prevent ADM-induced renal vasodilation supports the hypoth esis of ADM altering renal hemodynamics by interacting with ADM- and n ot CGRP-specific membrane receptors.