Inhibition of nitric oxide synthase enhances superoxide activity in canine kidney

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Abstract
To evaluate the role of a potential interaction between superoxide anion (O2−) 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, Nω-nitro-l-arginine (NLA; 50 μg·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 μl·min−1·g−1), or sodium excretion (UNaV; 2.4 ± 0.3 to 2.2 ± 0.3 μmol·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 μl·min−1·g−1) and in UNaV (0.7 ± 0.1 to 1.3 ± 0.2 μmol·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 O2−levels and support the hypothesis that NO plays a protective role against the actions of O2−in the kidney.