SELECTIVE A(1) ADENOSINE RECEPTOR ANTAGONISM AUGMENTS BETA-ADRENERGIC-INDUCED RENIN RELEASE IN-VIVO

This study determines, in vivo, whether endogenous adenosine/A(1) rece ptor interactions at juxtaglomerular cells restrain the release of ren in induced by receptor-mediated activation of the adenosine 3',5'-cycl ic monophosphate pathway and whether endogenous adenosine/A(2) recepto r interactions diminish this restraining response. The following four pharmacological probes were employed: 1) 1,3-dipropyl-8-cyclopentylxan thine (DPCPX) and 2) FK-453, both selective A(1) receptor antagonists; 3) FR-113452, a nearly inactive enantiomer of FK-453; and 4) KF-17837 , a selective A(2) receptor blocker. Adult Sprague-Dawley rats were pr epared (adrenalectomized, renal denervated, uninephrectomized, and tre ated with indomethacin, aldosterone, and hydrocortisone) to minimize e ndogenous stimulation of renin release and received either vehicle (co ntrol group) or one of the four drugs. Intrarenal infusions of isoprot erenol (3, 30, and 100 ng . kg(-1). min(-1)) caused dose-related incre ases in plasma renin activity (PRA). This PRA response was significant ly augmented in the groups receiving DPCPX (P = 0.0010) or FK-453 (P = 0.0001) but was not altered in the groups treated with FR-113452 (P = 0.3422) or KF-17837 (P = 0.2155). Systemic and renal hemodynamics and renal electrolyte excretions were monitored and could not account for the PRA augmentation caused by the A(1) antagonists. This study clear ly demonstrates that endogenous adenosine acts on the A(1) receptor to restrain the renin release induced by activation of intrarenal beta-a drenoceptors and is not counteracted by endogenous activation of the A (2) receptor.