Inhibition of nitric oxide synthase enhances superoxide activity in canine kidney

To evaluate the role of a potential interaction between superoxide anion (O-2(-)) and nitric oxide (NO) in regulating kidney function, we examined the renal responses to intra-arterial infusion of a superoxide dismutase mimetic, tempol (0.5 mg.kg(-1).min(-1)), in anesthetized dogs treated with or without NO synthase inhibitor, Nomega-nitro-L-arginine (NLA; 50 mug.kg(-1).min(-1)). In one group of dogs (n=10), tempol infusion alone for 30 min before NLA infusion did not cause any significant changes in renal blood flow (RBF; 5.2+/-0.4 to 5.0+/-0.4 ml.min(-1).g(-1)), glomerular filtration rate (GFR; 0.79+/-0.04 to 0.77+/-0.04 ml.min(-1).g(-1)), urine flow (V; 13.6+/-2.1 to 13.9+/-2.5 mul.min(-1).g(-1)), or sodium excretion (UNaV; 2.4+/-0.3 to 2.2+/-0.3 mumol.min(-1).g(-1)). Interestingly, when tempol was infused in another group of dogs (n=12) pretreated with NLA, it caused increases in V (4.4+/-0.4 to 9.7+/-1.4 mul.min(-1).g(-1)) and in UNaV (0.7+/-0.1 to 1.3+/-0.2 mumol.min(-1).g(-1)) without affecting RBF or GFR. Although NO inhibition caused usual qualitative responses in both groups of dogs, the antidiuretic (47+/-5 vs. 26+/-4%) and antinatriuretic (67+/-4 vs. 45+/-11%) responses to NLA were seen much less in dogs pretreated with tempol. NLA infusion alone increased urinary excretion of 8-isoprostane (13.9+/-2.7 to 22.8+/-3.6 pg.min(-1).g(-1); n=7), which returned to the control levels (11.6+/-3.4 pg.min(-1).g-(1)) during coadministration of tempol. These data suggest that NO synthase inhibition causes enhancement of endogenous O-2(-) levels and support the hypothesis that NO plays a protective role against the actions of O-2(-) in the kidney.