HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 296/1/F170    most recent 90487.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Matavelli, L. C. Articles by Majid, D. S. A. Search for Related Content PubMed PubMed Citation Articles by Matavelli, L. C. Articles by Majid, D. S. A.

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

Departments of ¹Physiology and ²Pharmacology, Hypertension and Renal Center of Excellence, Tulane University Health Sciences Center, New Orleans, Louisiana

Submitted 13 August 2008 ; accepted in final form 3 November 2008

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 (U_NaV) 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 U_NaV. 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.

nitric oxide; superoxide; oxidative stress; renal blood flow; glomerular filtration rate