Angiotensin II and nitric oxide in neural control of intrarenal blood flow

Department of Physiology, Monash University, Melbourne, Victoria, Australia Submitted 16 July 2004 ; accepted in final form 29 April 2005 We investigated the roles of the renin-angiotensin system and the significance of interactions between angiotensin II and nitric oxide, in responses of regional kidney perfusion to electrical renal nerve stimulation (RNS) in pentobarbital sodium-anesthetized rabbits. Under control conditions, RNS (0.5–8 Hz) reduced total renal blood flow (RBF; –89 ± 3% at 8 Hz) and cortical perfusion (CBF; –90 ± 2% at 8 Hz) more than medullary perfusion (MBF; –55 ± 5% at 8 Hz). Angiotensin II type 1 (AT 1 )-receptor antagonism (candesartan) blunted RNS-induced reductions in RBF ( P = 0.03), CBF ( P = 0.007), and MBF ( P = 0.04), particularly at 4 and 8 Hz. Nitric oxide synthase inhibition with N G -nitro- L -arginine ( L -NNA) enhanced RBF ( P = 0.003), CBF ( P = 0.001), and MBF ( P = 0.03) responses to RNS, particularly at frequencies of 2 Hz and less. After candesartan pretreatment, L -NNA significantly enhanced RNS-induced reductions in RBF ( P = 0.04) and CBF ( P = 0.007) but not MBF ( P = 0.66). Renal arterial infusion of angiotensin II (5 ng·kg –1 ·min –1 ) selectively enhanced responses of MBF to RNS in L -NNA-pretreated but not in vehicle-pretreated rabbits. In contrast, greater doses of angiotensin II (5–15 ng·kg –1 ·min –1 ) blunted responses of MBF to RNS in rabbits with intact nitric oxide synthase. These results suggest that endogenous angiotensin II enhances, whereas nitric oxide blunts, neurally mediated vasoconstriction in the renal cortical and medullary circulations. In the renal medulla, but not the cortex, angiotensin II also appears to be able to blunt neurally mediated vasoconstriction. renal medullary blood flow; renal cortical blood flow; sympathetic nervous system Address for reprint requests and other correspondence: R. G. Evans, Dept. of Physiology, PO Box 13F, Monash Univ., Melbourne, Victoria 3800, Australia (e-mail: roger.evans{at}med.monash.edu.au )