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(Circulation Research. 2004;95:122.)
© 2004 American Heart Association, Inc.

Editorials

And What About the Endothelium?

On the Predominance of Cerebral Superoxide Formation for Angiotensin II–Induced Systemic Hypertension

Ralf P. Brandes

From the Institut für Kardiovaskuläre Physiologie Klinikum der J.W. Goethe-Universität, Theodor-Stern-Kai 7 D-60596, Frankfurt am Main, Germany.

Correspondence to Ralf P. Brandes, Institut für Kardiovaskuläre Physiologie Klinikum der J.W. Goethe-Universität Theodor-Stern-Kai 7 D-60596, Frankfurt am Main, Germany. E-mail r.brandes@em.uni-frankfurt.de

See related article, pages 210–216

Key Words: superoxide dismutase • oxidative stress • angiotensin II • hypertension • NADPH oxidase

An extract of the first 250 words of the full text is provided, because this article has no abstract.

The hypertensive action of angiotensin II (Ang II) is a consequence of its effects on the kidney, the nervous system, and the vasculature resulting in direct vasoconstriction, increase in sympathetic outflow and sodium and water retention. In addition to these effects, Ang II enhances the generation of superoxide anions (O₂^–) within the vasculature by inducing and activating NADPH oxidases.¹ O₂^– rapidly reacts with nitric oxide (NO) and thereby limits the bioavailability of this endogenous vasodilator. The reaction product of O₂^– and NO, peroxynitrite, is a highly aggressive compound that oxidizes proteins, lipids, and enzyme cofactors.¹ Therefore, one important consequence of increased plasma levels of Ang II is endothelial dysfunction, usually identified as an attenuated endothelium-dependent, NO-mediated vasodilatation. Under normal conditions, the endothelium continuously releases NO in response to fluid shear stress and endothelium-derived NO continuously and significantly lowers vascular resistance. The loss of this "basal" NO production in endothelial NO synthase knockout mice (eNOS^–/–) mice is thought to underlie the hypertensive phenotype in these animals. The logical consequence of this is that the scavenging of NO by O₂^– during Ang II treatment may increase peripheral resistance and thus contribute to hypertension.¹

The study by Zimmermann et al² in this issue of Circulation Research challenges the physiological importance of this paradigm and reminds us of the extraordinary role of the nervous system in the control of blood pressure.² In this article, which is part of a series of articles from the same group,^3–6 the authors provide another piece of . . . [Full Text of this Article]