The effects of NG-nitro-L-arginine, a nitric oxide synthase inhibitor, on norepinephrine overflow and antidiuresis induced by stimulation of renal nerves in anesthetized dogs
Egi, Y.; Matsumura, Y.; Murata, S.; Umekawa, T.; Hisaki, K.; Takaoka, M.; Morimoto, S.
Journal of Pharmacology and Experimental Therapeutics 269(2): 529-535
1994
ISSN/ISBN: 0022-3565 PMID: 7514219 Document Number: 432161
We examined the involvement of endogenous nitric oxide (NO) in noradrenergic neurotransmission and renal function in anesthetized dogs, by using NG-nitro-L-arginine (NOARG), a NO synthase inhibitor. Renal nerve stimulation (RNS) produced the frequency-dependent increase in the rate of norepinephrine secretion. The low frequency RNS (0.5-2.0 Hz) decreased urine flow and urinary excretion of sodium, without affecting renal hemodynamics. High frequency RNS (2.5-5.0 Hz) caused a more potent antidiuresis and renal vasoconstriction that resulted in reductions in renal blood flow and glomerular filtration rate. Intrarenal arterial infusion of NOARG, at a dose (10 micrograms/kg/min) which had no effect on renal hemodynamics, significantly enhanced the RNS-induced reductions of urine formation and renal vasoconstriction and increments in norepinephrine secretion rate. Qualitatively similar results were observed with a higher dose of NOARG (40 micrograms/kg/min), although this dose did decrease basal levels of renal blood flow and urine flow. Enhancement of NOARG on RNS-induced actions was abolished by the simultaneous administration of L-arginine. Endogenous NO probably has a role as inhibitory modulator of renal noradrenergic neurotransmission.