Nitric oxide blockade enhances renal responses to superoxide dismutase inhibition in dogs

To examine the potential role of superoxide anion (O-2(-)) and its interaction with NO in the regulation of renal hemodynamics and excretory function, we have evaluated the renal responses to enhancement in O-2(-) activity before and during NO synthase inhibition in anesthetized dogs (n=6). Intraarterial infusion of a superoxide dismutase (SOD) inhibitor, diethyldithiocarbamate (DETC; 0.1 and 0.5 mg/kg per min) was made to enhance O-2(-) activity in the kidney. Cortical (CBF), medullary (MBF), and total renal blood flow (RBF) responses were assessed using laser-Doppler needle flow probes and an electromagnetic flow probe. DETC caused dose-dependent changes in renal parameters, which were recovered within 30 minutes after the termination of DETC infusion. The high-dose infusion of DETC for 25 minutes resulted in an increase of 29+/-10% in renal vascular resistance (control, 35.4+/-4.4 mm Hg/mL per min per g) and decreases of 21+/-5% in RBF (control, 3.5 x 0.5 mL/min per g), 20+/-5% in CBF, 21+/-7% in MBF, 62+/-11% in urine flow (control, 10.5+/-2.2 muL/min per g), and 47+/-11% in sodium excretion (control, 2.1+/-0.2 mumol/min per g), without a significant change (-10+/-6%) in glomerular filtration rate (control, 0.74+/-0.09 mL/min per g). During NO synthase inhibition with intraarterial administration of nitro-L-arginine (50 mug/kg per min), the same dose of DETC showed a greater increase in renal vascular resistance (73+/-15%) and reductions in RBF (39+/-4%), CBF (32+/-5%), MBF (34+/-6%), urine flow (78+/-5%), and sodium excretion (67+/-10%), with a marked reduction in glomerular filtration rate (59+/-7%). These data indicate that O-2(-) exerts renal vasoconstriction as well as antidiuretic and antinatriuretic effects. These responses are enhanced during NO synthase blockade, suggesting that NO serves a renoprotective effect against these action of O-2(-).