And what about the endothelium? On the predominance of cerebral superoxide formation for angiotensin II-induced systemic hypertension.

Abstract

See related article, pages 210–216 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 information to substantiate their proposal that Ang II–induced hypertension is predominantly the consequence of cerebral redox-mediated regulatory processes. They demonstrate that Ang II–dependent O2− production is not restricted to the …