INTERACTIVE CONTROL OF RENAL-FUNCTION BY ALPHA(2)-ADRENERGIC SYSTEM AND NITRIC-OXIDE - ROLE OF ANGIOTENSIN-II

We studied the role of angiotensin II (AII) in the interactive control of renal function by the alpha(2)-adrenergic system and nitric oxide (NO) in adult male Munich Wistar rats 5-7 days after ipsilateral renal denervation (DNX). Renal micropuncture was used under euvolemic condi tions before (period 1) and during (period 2) systemic inhibition of N O synthase (NOS) with N-G-monomethyl-L-arginine (L-NMMA) in three grou ps, Group 1 served as a DNX control. In group 2, the alpha(2)-adrenerg ic agonist B-HT 933 (BHT) was infused systemically throughout the expe riment. In group 3, the AII-receptor blocker, Iosartan (LOS), was infu sed before period 2 as well as throughout infusion of BHT. L-NMMA incr eased blood pressure (BP) to a similar degree in all three groups. In group I, infusion of L-NMMA did not affect glomerular hemodynamics or tubular function. With BHT in group 2, L-NMMA reduced absolute proxima l tubular reabsorption (APR) and by reducing nephron plasma flow (SNPF ) and glomerular ultrafiltration coefficient (LpA) caused nephron filt ration rate (SNGFR) to decrease, a response described in innervated ki dneys. LOS in group 3 abrogated the BHT-facilitated reduction of LpA a nd SNGFR but not of SNPF and APR in response to L-NMMA. In group 1, ur inary sodium excretion (UNaV) did not change and urinary flow rate (UV ) increased slightly in period 2. L-NMMA combined with BHT, however, e xerted a profound diuresis and natriuresis in group 2. These effects w ere further exaggerated with LOS. In a fourth group of DNX rats, LOS g iven alone before period 2 did not affect SNGFR, SNPF, LpA, APR, UV, o r UNaV, We conclude that after subacute renal denervation alpha(2)-adr energic activation sensitizes (a) LpA to reduction by NOS inhibition t hrough an AII-dependent mechanism, and (b) SNPF and proximal tubular r eabsorption to reduction by L-NMMA regardless of the AII activity. Fur thermore, our results suggest a potential role for the alpha(2)-adrene rgic system and AII in the diuretic and natriuretic effect of systemic NOS inhibition.