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 +/- 0.5 mL/min per g), 20 +/- 5% in CBF, 21 +/- 7% in MBF, 62 +/- 11% in urine flow (control, 10.5 +/- 2.2 microL/min per g), and 47 +/- 11% in sodium excretion (control, 2.1 +/- 0.2 micromol/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 microg/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 +/- 0%), 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)(-).