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 (O(2)(-)). 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 microg.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 microg.kg(-1).min(-1)) of OONO(-) increased RBF by 10 +/- 3% and GFR by 15 +/- 5%. The higher doses (20 and 40 microg.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 (U(Na)V) during OONO(-) infusion. However, in rats pretreated with NO synthase (NOS) inhibitor, l-NAME (50 microg.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 U(Na)V. Long-term infusion of OONO(-) (10 microg.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.
Matavelli
Luis C
LC
Dept. of Physiology, Tulane Univ. Health Sciences Center, 1430 Tulane Ave., SL 39, New Orleans, LA 70112, USA.
Kadowitz
Philip J
PJ
Navar
L Gabriel
LG
Majid
Dewan S A
DS
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005919:Glomerular Filtration Rate / Q000187:drug effects* / Q000502:physiology; D007261:Infusions, Intra-Arterial; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000502:physiology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D030421:Peroxynitrous Acid / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects* / Q000502:physiology; D014474:Unconsciousness; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
D004791:Enzyme Inhibitors; D030421:Peroxynitrous Acid; D019331:NG-Nitroarginine Methyl Ester