Submitted on August 13, 2008
Revised on October 23, 2008
Accepted on November 3, 2008
Renal hemodynamic and excretory responses to intra-arterial infusion of peroxynitrite in anesthetized rats
Luis C Matavelli1, Philip J Kadowitz2, L. Gabriel Navar3, and Dewan S.A. Majid3*
1 Tulane University Health Sciences Center
2 Tulane University, Health Sciences Center
3 Tulane University School of Medicine
* To whom correspondence should be addressed. E-mail: majid{at}tulane.edu.
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/min; 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/min) of OONO- increased RBF by 10 ± 3% and GFR by 15 ± 5%. The higher doses (20 and 40 µg/kg/min) 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 pre-treated with NO synthase (NOS) inhibitor, L-NAME (50 µg/kg/min; 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/min 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 reno-protective function at low concentration that depends on intact NOS activity.
