CALL FOR PAPERS Oxidative Stress Inhibition of nitric oxide synthase enhances superoxide activity in canine kidney

Majid, Dewan S. A., Akira Nishiyama, Keith E. Jackson, and Alexander Castillo. Inhibition of nitric oxide synthase enhances superoxide activity in canine kidney. Am J Physiol Regul Integr Comp Physiol 287: R27–R32, 2004. First published March 25, 2004; 10.1152/ajpregu.00073.2004.—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 ), in anesthetized dogs treated with or without NO synthase inhibitor, N -nitro-L-arginine (NLA; 50 g kg 1 min ). 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 ), glomerular filtration rate (GFR; 0.79 0.04 to 0.77 0.04 ml min 1 g ), urine flow (V; 13.6 2.1 to 13.9 2.5 l min 1 g ), or sodium excretion (UNaV; 2.4 0.3 to 2.2 0.3 mol min 1 g ). 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 l min 1 g ) and in UNaV (0.7 0.1 to 1.3 0.2 mol min 1 g ) 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 ; n 7), which returned to the control levels (11.6 3.4 pg min 1 g ) 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.