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 conditions before (period 1) and during (period 2) systemic inhibition of NO synthase (NOS) with N-G-monomethyl-L-arginine (L-NMMA) in three groups, Group 1 served as a DNX control. In group 2, the alpha(2)-adrenergic agonist B-HT 933 (BHT) was infused systemically throughout the experiment. In group 3, the AII-receptor blocker, Iosartan (LOS), was infused before period 2 as well as throughout infusion of BHT. L-NMMA increased 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 proximal tubular reabsorption (APR) and by reducing nephron plasma flow (SNPF) and glomerular ultrafiltration coefficient (LpA) caused nephron filtration rate (SNGFR) to decrease, a response described in innervated kidneys. LOS in group 3 abrogated the BHT-facilitated reduction of LpA and SNGFR but not of SNPF and APR in response to L-NMMA. In group 1, urinary sodium excretion (UNaV) did not change and urinary flow rate (UV) increased slightly in period 2. L-NMMA combined with BHT, however, exerted a profound diuresis and natriuresis in group 2. These effects were further exaggerated with LOS. In a fourth group of DNX rats, LOS given alone before period 2 did not affect SNGFR, SNPF, LpA, APR, UV, or UNaV, We conclude that after subacute renal denervation alpha(2)-adrenergic activation sensitizes (a) LpA to reduction by NOS inhibition through an AII-dependent mechanism, and (b) SNPF and proximal tubular reabsorption to reduction by L-NMMA regardless of the AII activity. Furthermore, our results suggest a potential role for the alpha(2)-adrenergic system and AII in the diuretic and natriuretic effect of systemic NOS inhibition.