An inducible nitric oxide synthase has recently been described in proximal tubule epithelium. To investigate the effects of proximal tubule NO on Na+/K+-ATPase, we induced NO production in mouse proximal tubule epithelial cells by treatment with lipopolysaccharide (LPS) and interferon-y (IFNy) followed by determinations of ouabain-sensitive ATPase activity. Na+/K+-ATPase activity decreased after 4 h of LPS/IFNy treatment, reaching maximal inhibition after 24 h (34% reduction in activity). The inhibition of Na+/K+-ATPase activity by LPS/IFNy was prevented by simultaneous incubation with Nw-nitro L-arginine and markedly blunted by removal of L-arginine from the medium. The NO donors sodium nitroprusside and SIN-1 also inhibited Na+/K+-ATPase activity to a similar extent than LPS/IFNy. However, treatment with 8-pCPT-cGMP only modestly reduced Na+/K+-ATPase activity. Interestingly, superoxide dismutase prevented the inhibitory effects of NO on Na+/K+-ATPase activity, suggesting a role for peroxynitrite in this inhibition. We conclude that NO generated by mouse proximal tubule epithelial cell iNOS inhibits Na/K ATPase activity in an autocrine fashion and that this inhibition is accompanied by a reduction in Na-dependent solute transport. (J. Clin. Invest. 1995. 95
LGG provided by the enteral route is able to downregulate LPS-induced proinflammatory mediators. This effect is not only present in the splanchnic organs, that is, the intestine and the liver, but extends to the plasma and a distal organ, the lung.
Decoy ODN-based techniques effectively inhibit iNOS expression in renal epithelium and represent a potentially useful approach for selective blockade of this enzyme in pathologic conditions associated with excessive NO production.
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