Nitric oxide - superoxide cooperation in the regulation of renal Naplus, Kplus -ATPase

• Autorzy: Beltowski J. , Marciniak A. , Jamroz-Wisniewska A. , Borkowska E.
• Języki publikacji: EN

Abstrakty

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 umol/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 ^mol/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.

Słowa kluczowe

EN

pathogenesis; nitric oxide; oxidative stress; reactive oxygen species; arterial hypertension; superoxide anion

• Wydawca: -
• Czasopismo: Acta Biochimica Polonica
• Rocznik: 2004
• Tom: 51
• Numer: 4
• Opis fizyczny: p.933-942,fig.,ref.

Twórcy

autor

Beltowski J.

• Medical University, K.Jaczewskiego 8, 20-090 Lublin, Poland

autor

Marciniak A.

autor

Jamroz-Wisniewska A.

autor

Borkowska E.

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