Facilitatory role of NO in neural norepinephrine release in the rat kidney

We examined modulation by nitric oxide (NO) of sympathetic neurotransmitter release and vasoconstriction in the isolated pump-perfused rat kidney. Electrical renal nerve stimulation (RNS; 1 and 2 Hz) increased renal perfusion pressure and renal norepinephrine (NE) efflux. Nonselective NO syn-thase (NOS) inhibitors [N-nitro-L-arginine methyl ester (L-NAME) or N-nitro-L-arginine], but not a selective neu-ronal NO synthase inhibitor (7-nitroindazole sodium salt), suppressed the NE efflux response and enhanced the per-fusion pressure response. Pretreatment with L-arginine prevented the effects of L-NAME on the RNS-induced re-sponses. 2-(4-Carboxyphenyl)-4,4,5,5-tetramethylimidazo-line-1-oxyl-3-oxide (carboxy-PTIO), which eliminates NO by oxidizing it to NO2, suppressed the NE efflux response, whereas the perfusion pressure response was less suscep-tible to carboxy-PTIO. 8-Bromoguanosine cGMP sup-pressed and a guanylate cyclase inhibitor [4H-8-bromo-1,2,4-oxadiazolo(3,4-d)benz(b)(1,4)oxazin-1-one] enhanced the RNS-induced perfusion pressure response, but neither of these drugs affected the NE efflux response. These results suggest that endogenous NO facilitates the NE release through cGMP-independent mechanisms, NO metabolites formed after NO2 rather than NO itself counteract the vaso-constriction, and neuronal NOS does not contribute to these modulatory mechanisms in the sympathetic nervous system of the rat kidney. sympathetic nerves; vasoconstriction; nitric oxide synthase inhibitor; guanylate cyclase inhibitor; nitric oxide scavenger NITRIC OXIDE (NO) participates in various kinds of phys-iological responses through elevation of intracellular cGMP level by activating soluble guanylate cyclas