Inhibition of nitric oxide synthase enhances superoxide activity in canine kidney. To evaluate the role of a potential interaction between superoxide anion (O 2 Ϫ ) 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 ⅐ kg Ϫ1 ⅐ min Ϫ1 ), in anesthetized dogs treated with or without NO synthase inhibitor, N -nitro-L-arginine (NLA; 50 g ⅐ kg Ϫ1 ⅐ min Ϫ1 ). In one group of dogs (n ϭ 10),

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... pol infusion alone for 30 min before NLA infusion did not cause any significant changes in renal blood flow (RBF; 5.2 Ϯ 0.4 to 5.0 Ϯ 0.4 ml ⅐ min Ϫ1 ⅐ g Ϫ1 ), glomerular filtration rate (GFR; 0.79 Ϯ 0.04 to 0.77 Ϯ 0.04 ml ⅐ min Ϫ1 ⅐ g Ϫ1 ), urine flow (V; 13.6 Ϯ 2.1 to 13.9 Ϯ 2.5 l ⅐ min Ϫ1 ⅐ g Ϫ1 ), or sodium excretion (UNaV; 2.4 Ϯ 0.3 to 2.2 Ϯ 0.3 mol ⅐ min Ϫ1 ⅐ g Ϫ1 ). Interestingly, when tempol was infused in another group of dogs (n ϭ 12) pretreated with NLA, it caused increases in V (4.4 Ϯ 0.4 to 9.7 Ϯ 1.4 l⅐min Ϫ1 ⅐g Ϫ1 ) and in UNaV (0.7 Ϯ 0.1 to 1.3 Ϯ 0.2 mol⅐min Ϫ1 ⅐g Ϫ1 ) without affecting RBF or GFR. Although NO inhibition caused usual qualitative responses in both groups of dogs, the antidiuretic (47 Ϯ 5 vs. 26 Ϯ 4%) and antinatriuretic (67 Ϯ 4 vs. 45 Ϯ 11%) responses to NLA were seen much less in dogs pretreated with tempol. NLA infusion alone increased urinary excretion of 8-isoprostane (13.9 Ϯ 2.7 to 22.8 Ϯ 3.6 pg ⅐ min Ϫ1 ⅐ g Ϫ1 ; n ϭ 7), which returned to the control levels (11.6 Ϯ 3.4 pg ⅐ min Ϫ1 ⅐ g Ϫ1 ) during coadministration of tempol. These data suggest that NO synthase inhibition causes enhancement of endogenous O 2 Ϫ levels and support the hypothesis that NO plays a protective role against the actions of O 2