Selective a1 adenosine receptor antagonism augments [beta]
-adrenergic-induced renin release in vivo.
Pfeifer, Cynthia A., Fumio Suzuki, and Edwin K. Jackson.
Center for Clinical Pharmacology, University of Pittsburgh Medical
Center, Pittsburgh, PA, USA and Kyowa Hakko Kogyo Co., Ltd.,
Shizuoka-Ken, Japan
APStracts 2:0051F, 1995.
This study determines, in vivo, whether endogenous adenosine/A1
receptor interactions at juxtaglomerular cells restrain the release
of renin induced by receptor-mediated activation of the cyclic AMP
pathway, and whether endogenous adenosine/A2 receptor interactions
diminish this restraining response. Four pharmacological probes were
employed: 1) DPCPX and 2) FK453, selective A1 receptor antagonists;
3) FR113452, a nearly inactive enantiomer of FK453; and 4) KF17837, a
selective A2 receptor blocker. Adult Sprague-Dawley rats were
prepared (adrenalectomized, renal denervated, uninephrectomized, and
treated with indomethacin, aldosterone and hydrocortisone) to
minimize endogenous stimulation of renin release, and received either
vehicle (control group) or one of the 4 drugs. Intrarenal infusions
of isoproterenol (3, 30 and 100 ng/kg/min) caused dose-related
increases in plasma renin activity (PRA). This PRA response was
significantly augmented in the groups receiving DPCPX (p=0.0010) or
FK453 (p=0.0001), but was not altered in the groups treated with
FR113452 (p=0.3422) or KF17837 (p=0.2155). Systemic and renal
hemodynamics and renal electrolyte excretions were monitored and
could not account for the PRA augmentation caused by the A1
antagonists. This study clearly demonstrates that endogenous
adenosine acts on the A1 receptor to restrain the renin release
induced by activation of intrarenal [beta]-adrenoceptors and is not
counteracted by endogenous activation of the A2 receptor.
Received 10 February 1995; accepted in final form 5 April 1995.
APS Manuscript Number F50-5.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 19 April 1995.