Nitric oxide -- superoxide cooperation in the regulation of renal Na(+),K(+)-ATPase.
Journal Title: Acta Biochimica Polonica - Year 2004, Vol 51, Issue 4
Abstract
The aim of this study was to investigate whether endogenous superoxideanion is involved in the regulation of renal Na(+),K(+)-ATPase and ouabain-sensitive H(+),K(+)-ATPaseactivities. The study was performed in male Wistar rats. Compounds modulating superoxide anion concentrationwere infused under general anaesthesia into the abdominal aorta proximally to the renal arteries. Theactivity of ATPases was assayed in isolated microsomal fraction. We found that infusion of a superoxideanion-generating mixture, xanthine oxidase (1 mU/min per kg) + hypoxanthine (0.2 mumol/min per kg), increasedthe medullary Na(+),K(+)-ATPase activity by 49.5% but had no effect on cortical Na(+),K(+)-ATPase andeither cortical or medullary ouabain-sensitive H(+),K(+)-ATPase. This effect was reproduced by elevatingendogenous superoxide anion with a superoxide dismutase inhibitor, diethylthiocarbamate. In contrast,a superoxide dismutase mimetic, TEMPOL, decreased the medullary Na(+),K(+)-ATPase activity. The inhibitoryeffect of TEMPOL was abolished by inhibitors of nitric oxide synthase (L-NAME), soluble guanylate cyclase(ODQ) and protein kinase G (KT5823). The stimulatory effect of diethylthiocarbamate was not observedin animals pretreated with a synthetic cGMP analogue, 8-bromo-cGMP. An inhibitor of NAD(P)H oxidase,apocynin (1 mumol/min per kg), decreased the Na(+),K(+)-ATPase activity in the renal medulla and itseffect was prevented by L-NAME, ODQ or KT5823. In contrast, a xanthine oxidase inhibitor, oxypurinol,administered at the same dose was without effect. These data suggest that NAD(P)H oxidase-derived superoxideanion increases Na(+),K(+)-ATPase activity in the renal medulla by reducing the availability of NO. Excessiveintrarenal generation of superoxide anion may upregulate medullary Na(+),K(+)-ATPase leading to sodiumretention and blood pressure elevation.
Authors and Affiliations
Ewelina Borkowska, Anna Jamroz-Wiśniewska, Andrzej Marciniak, Jerzy Bełtowski
Keywords
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