EFFECTS OF FK409, A NITRIC-OXIDE DONOR, ON RENAL RESPONSES TO RENAL NERVE-STIMULATION IN ANESTHETIZED DOGS

We examined the effects of -4-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hex enamide (FK409), a nitric oxide (NO) donor, on renal actions and norep inephrine overflow induced by renal nerve stimulation in anesthetized dogs, with or without N-G-nitro-L-arginine (NOARG), a NO synthase inhi bitor. Renal nerve stimulation at a low frequency (0.5-2.0 Hz) produce d significant decreases in urine flow and urinary excretion of Na+ and increases in norepinephrine secretion rate. Renal nerve stimulation a t a high frequency (2.5-5.0 Hz) which diminishes renal hemodynamics, e licited more marked decreases in urine formation and increases in nore pinephrine secretion rate. Intrarenal arterial infusion of FK409 (0.25 mu g/kg/min) failed to alter renal actions and increases in norepinep hrine secretion rate in response to both low-and high frequency renal nerve stimulation. When NOARG (40 mu g/kg/min) was administrated intra renally, low-frequency renal nerve stimulation caused a potent antidiu resis and renal vasoconstriction. The renal nerve stimulation-induced increase in norepinephrine secretion rate was markedly enhanced by NOA RG infusion. Simultaneous infusion of FK409 markedly attenuated the NO ARG-induced enhancement of renal actions and increases in norepinephri ne secretion rate, in response to low-frequency renal nerve stimulatio n. These results suggest that exogenous NO suppresses the renal nerve stimulation-induced norepinephrine overflow and renal actions in NO-de pleted conditions. We also propose that endogenous NO functions tonica lly as an inhibitory modulator of renal noradrenergic neurotransmissio n. (C) 1998 Elsevier Science B.V.