Renal hemodynamic and excretory responses to intra-arterial infusion of peroxynitrite in anesthetized rats

• Published in: American Journal of Physiology - Renal Physiology Vol. 296; no. 1; pp. F170 - F176
• Main Authors: Matavelli, Luis C, Kadowitz, Philip J, Navar, L Gabriel, Majid, Dewan S A
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.01.2009
• Subjects: Animals; Blood; Dose-Response Relationship, Drug; Enzyme Inhibitors - pharmacology; Glomerular Filtration Rate - drug effects; Glomerular Filtration Rate - physiology; Infusions, Intra-Arterial; Ions; Kidney - blood supply; Kidney - drug effects; Kidney - physiology; Kidney diseases; Male; NG-Nitroarginine Methyl Ester - pharmacology; Nitric oxide; Peroxynitrous Acid - administration & dosage; Peroxynitrous Acid - pharmacology; Physiology; Proteins; Rats; Rats, Sprague-Dawley; Regional Blood Flow - drug effects; Regional Blood Flow - physiology; Rodents; Unconsciousness; Vasoconstriction - drug effects; Vasoconstriction - physiology; Vasodilation - drug effects; Vasodilation - physiology
• ISSN: 1931-857X; 0363-6127; 1522-1466
• DOI: 10.1152/ajprenal.90487.2008

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.