Published Online
on November 3, 2003

A more recent version of this article appeared on December 1, 2003

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Submitted on August 6, 2003
Revised on August 19, 2003

Role of Superoxide in Modulating the Renal Effects of Angiotensin II

Bernardo López; Miguel García Salom; Begoña Arregui; Fernando Valero; and Francisco J. Fenoy^*

From Departamento de Fisiología, Facultad de Medicina, Universidad de Murcia, 30100-Murcia, Spain.

^* To whom correspondence should be addressed. E-mail: fjfenoy{at}um.es.

Abstract--Angiotensin II is known to stimulate NADPH oxidase-dependent superoxide (O₂^-) generation, which may contribute to the acute renal vasoconstrictor and antinatriuretic actions of this peptide. To evaluate this hypothesis, the effects of a superoxide dismutase mimetic (tempol) or a NADPH inhibitor (apocynin) on the angiotensin renal actions were studied. Renal cortical nitric oxide (NO) was measured electrochemically in vivo. Tempol increased sodium excretion and NO levels. Apocynin raised renal blood flow, glomerular filtration rate, sodium excretion, and NO levels. These results indicate the presence of an endogenous NADPH oxidase-dependent O₂^- generation that may modulate renal function by scavenging NO. Angiotensin II infusion reduced renal blood flow, glomerular filtration, sodium excretion, and NO levels in a dose-dependent manner. The angiotensin receptor antagonist valsartan, tempol, or apocynin blunted the angiotensin effects on renal excretion and NO, suggesting that angiotensin receptors stimulation induces the NADPH oxidase-dependent O₂^- generation that might reduce NO bioavailability. This idea is supported by the finding that angiotensin increased O₂^- generation in renal homogenates, and this effect was prevented by valsartan, apocynin, or tempol. These results indicate that some of the acute renal effects of angiotensin II may be enhanced by an increased NADPH oxidase-derived O₂^- production that reduces renal NO bioavailability.

Key words: antioxidants • kidney • oxygen • nitric oxide • angiotensin II

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