Renal hemodynamic and excretory responses to intra-arterial infusion of peroxynitrite in anesthetized rats
Peroxynitrite (ONOO−) is formed endogenously by the reaction of nitric oxide (NO) and superoxide (O2−). To examine the hypothesis that OONO− cause renal vasodilation at low concentrations but cause vasoconstriction at higher concentrations, we examined renal responses to intra-arterial infusion of incremental doses of OONO− (10, 20, and 40 μg·kg−1·min−1; 45 min each) in anesthetized rats. Renal blood flow (RBF) and glomerular filtration rate (GFR) were determined by PAH and inulin clearance. In control rats ( n = 6), low dose (10 μg·kg−1·min−1) of OONO− increased RBF by 10 ± 3% and GFR by 15 ± 5%. The higher doses (20 and 40 μg·kg−1·min−1) mostly reversed these responses which were −7 ± 4 and −27 ± 7% ( P < 0.05) in RBF and −0.1 ± 4.8 and −14 ± 12% in GFR, respectively. There were no appreciable changes in urine flow (V) and sodium excretion (UNaV) during OONO− infusion. However, in rats pretreated with NO synthase (NOS) inhibitor, l-NAME (50 μg·kg−1·min−1; n = 5), these doses of ONOO− significantly reduced RBF (−26 ± 7, −27 ± 6, and −44 ± 3%) and GFR (−21 ± 6, −25 ± 8, and −32 ± 12%) with variable increases in V or UNaV. Long-term infusion of OONO− (10 μg·kg−1·min−1 for 75 min) in another set of control rats ( n = 5) also showed similar vasodilator and hyperfiltration responses. These data indicate that ONOO− acts as an oxidant at high concentration but provides renoprotective function at low concentration that depends on intact NOS activity.