Superoxide generation by renal proximal tubule nitric oxide synthase

Nitric Oxide : Biology and Chemistry
L A Traylor, Philip R Mayeux

Abstract

Lipid A, the biologically active component of lipopolysaccharide, initiates a specific cytotoxic signaling cascade in the renal proximal tubule that involves a rapid release of intracellular calcium, the activation of nitric oxide synthase (NOS) and NO production. Superoxide (O2-) generation is also a component of this cascade and both NO and O2- are required for the development of oxidant stress and cytotoxicity. Here we examined whether NOS activity was responsible for O2- generation. In renal proximal tubules isolated from the rat, the NOS inhibitor N(G)-monomethyl-L-arginine (L-NMMA) but not D-NMMA blocked lipid A (50 microg/ml)-stimulated O2- generation as measured by the reduction of cytochrome c during a 30-min incubation period. When L-arginine (2 mM) was added to the tubule suspensions, O2- generation was significantly inhibited, while NO2- (a marker of NO generation) was significantly increased. The addition of L-arginine also reduced lipid A-stimulated malondialdehyde formation at 30 min (a marker of lipid peroxidation) and lactate dehydrogenase release at 90 min (a marker of cell death). Thus, lipid A-stimulated the generation of both NO and O2- via NOS activation. Furthermore, increasing L-arginine availability shi...Continue Reading

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Citations

Apr 19, 2003·Clinical and Experimental Pharmacology & Physiology·J López-MartíG Hotter
Aug 15, 2008·American Journal of Physiology. Renal Physiology·Matthew S ReifenbergerMark A Milanick
Dec 2, 2008·Biological & Pharmaceutical Bulletin·Tomomi KurashigeShigeru Kohno
Sep 8, 2010·Experimental Physiology·Steven E S MinerJohn D Parker
Aug 17, 2000·Nitric Oxide : Biology and Chemistry·D T Lowe
Feb 24, 2001·American Journal of Physiology. Renal Physiology·R Govers, T J Rabelink
Feb 22, 2001·American Journal of Physiology. Renal Physiology·C Zhang, P R Mayeux
Aug 15, 2002·Nitric Oxide : Biology and Chemistry·Chaojie ZhangPhilip R Mayeux

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