Effects of FK409, a nitric oxide donor, on renal responses to renal nerve stimulation in anesthetized dogs.
We examined the effects of (+/-)-(E)-4-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide (FK409), a nitric oxide (NO) donor, on renal actions and norepinephrine overflow induced by renal nerve stimulation in anesthetized dogs, with or without N(G)-nitro-L-arginine (NOARG), a NO synthase inhibitor. Renal nerve stimulation at a low frequency (0.5-2.0 Hz) produced significant decreases in urine flow and urinary excretion of Na+ and increases in norepinephrine secretion rate. Renal nerve stimulation at a high frequency (2.5-5.0 Hz) which diminishes renal hemodynamics, elicited more marked decreases in urine formation and increases in norepinephrine secretion rate. Intrarenal arterial infusion of FK409 (0.25 microg/kg/min) failed to alter renal actions and increases in norepinephrine secretion rate in response to both low- and high frequency renal nerve stimulation. When NOARG (40 microg/kg/min) was administrated intrarenally, low-frequency renal nerve stimulation caused a potent antidiuresis and renal vasoconstriction. The renal nerve stimulation-induced increase in norepinephrine secretion rate was markedly enhanced by NOARG infusion. Simultaneous infusion of FK409 markedly attenuated the NOARG-induced enhancement of renal actions and increases in norepinephrine secretion rate, in response to low-frequency renal nerve stimulation. These results suggest that exogenous NO suppresses the renal nerve stimulation-induced norepinephrine overflow and renal actions in NO-depleted conditions. We also propose that endogenous NO functions tonically as an inhibitory modulator of renal noradrenergic neurotransmission.
Tadano
K
K
Department of Pharmacology, Osaka University of Pharmaceutical Sciences, Takatsuki, Japan.
Matsuo
G
G
Hashimoto
T
T
Matsumura
Y
Y
D000758:Anesthesia; D000818:Animals; D004285:Dogs; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D007668:Kidney / Q000187:drug effects* / Q000294:innervation / Q000502:physiology; D008297:Male; D009474:Neurons / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism* / Q000652:urine; D009574:Nitro Compounds / Q000494:pharmacology*; D019335:Nitroarginine / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism*
D004791:Enzyme Inhibitors; D009574:Nitro Compounds; D019335:Nitroarginine; D009569:Nitric Oxide; C061872:FK 409; D009638:Norepinephrine