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 (U_NaV) 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 U_NaV 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.