Superoxide Formation and Interaction with Nitric Oxide Modulate Systemic Arterial Pressure and Renal Function in Salt-Depleted Dogs

Abstract

To determine the role of superoxide (O2–) formation in the kidney during alterations in the renin-angiotensin system, we evaluated responses to the intra-arterial infusion of an O2–-scavenging agent, tempol, in the denervated kidney of anesthetized salt-depleted (SD, n = 6) dogs and salt-replete (SR, n = 6) dogs. As expected, basal plasma renin activity was higher in SD than in SR dogs (8.4 ± 1.0 vs. 2.3 ± 0.6 ng angiotensin 1/ml/hr). Interestingly, the basal level of urinary F2-isoprostanes excretion (marker for endogenous O2– activity) relative to creatinine (Cr) excretion was also significantly higher in SD compared to SR dogs (9.1 ± 2.8 vs. 1.6 ± 0.4 ng F2-isoprostanes/mg of Cr). There was a significant increase in renal blood flow (4.3 ± 0.5 to 4.9 ± 0.6 ml/min/g) and decreases in renal vascular resistance (38.2 ± 5.8 to 33.2 ± 4.7 mm Hg/ml/min/g) and mean systemic arterial pressure (148 ± 6 to 112 ± 10 mm Hg) in SD dogs but not in SR dogs during infusion of tempol at 1 mg/kg/min for 30 mins. Glomerular filtration rate and urinary sodium excretion (UNaV) did not change significantly during tempol infusion in both groups of dogs. Administration of the nitric oxide synthase inhibitor nitro-L-arginine (50 μg/kg/min) during tempol infusion caused a reduction in UNaV in SR dogs (47% ± 12%) but did not cause a decrease in SD dogs. These data show that low salt intake enhances O2– activity that influences renal and systemic hemodynamics and thus may contribute to the regulation of arterial pressure in the salt-restricted state.