Nitric oxide - superoxide cooperation in the regulation of renal Na+,K+-ATPase.

• Authors: Jerzy Bełtowski , Andrzej Marciniak , Anna Jamroz-Wiśniewska , Ewelina Borkowska
• Languages of publication: EN

Abstracts

EN

The aim of this study was to investigate whether endogenous superoxide anion is involved in the regulation of renal Na+,K+-ATPase and ouabain-sensitive H+,K+-ATPase activities. The study was performed in male Wistar rats. Compounds modulating superoxide anion concentration were infused under general anaesthesia into the abdominal aorta proximally to the renal arteries. The activity of ATPases was assayed in isolated microsomal fraction. We found that infusion of a superoxide anion-generating mixture, xanthine oxidase (1 mU/min per kg) + hypoxanthine (0.2 μmol/min per kg), increased the medullary Na+,K+-ATPase activity by 49.5% but had no effect on cortical Na+,K+-ATPase and either cortical or medullary ouabain-sensitive H+,K+-ATPase. This effect was reproduced by elevating endogenous superoxide anion with a superoxide dismutase inhibitor, diethylthiocarbamate. In contrast, a superoxide dismutase mimetic, TEMPOL, decreased the medullary Na+,K+-ATPase activity. The inhibitory effect 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 observed in animals pretreated with a synthetic cGMP analogue, 8-bromo-cGMP. An inhibitor of NAD(P)H oxidase, apocynin (1 μmol/min per kg), decreased the Na+,K+-ATPase activity in the renal medulla and its effect 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 superoxide anion increases Na+,K+-ATPase activity in the renal medulla by reducing the availability of NO. Excessive intrarenal generation of superoxide anion may upregulate medullary Na+,K+-ATPase leading to sodium retention and blood pressure elevation.

Keywords

EN

H+,K+-ATPase; Sch 28080; superoxide anion; Na+,K+-ATPase; nitric oxide; oxidative stress

• Publisher: Polish Biochemical Society
• Journal: Acta Biochimica Polonica
• Year: 2004
• Volume: 51
• Issue: 4
• Pages: 933-942

Dates

published

2004

received

2004-06-23

revised

2004-10-01

accepted

2004-10-18

Contributors

author

Jerzy Bełtowski

• Department of Pathophysiology, Medical University, Lublin, Poland

author

Andrzej Marciniak

• Department of Pathophysiology, Medical University, Lublin, Poland

author

Anna Jamroz-Wiśniewska

• Department of Pathophysiology, Medical University, Lublin, Poland

author

Ewelina Borkowska

• Department of Pathophysiology, Medical University, Lublin, Poland

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