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(Hypertension. 2005;46:533.)
© 2005 American Heart Association, Inc.

Original Articles

Oxidative Stress Mediates Angiotensin II–Dependent Stimulation of Sympathetic Nerve Activity

From the Division of Nephrology, and the Hypertension Center, Keck School of Medicine, University of Southern California, Los Angeles.

Correspondence to Vito M. Campese, MD, Division of Nephrology and Hypertension Center, Keck School of Medicine, USC, 1200 N State St, Los Angeles, CA 90033. E-mail campese{at}usc.edu

Evidence indicates that angiotensin II (Ang II) enhances sympathetic nervous system (SNS) activity centrally and peripherally, but the exact mechanisms of this activation are not well established. We have previously shown that infusion of Ang II in the lateral cerebral ventricle raises blood pressure (BP), renal sympathetic nervous system activity (RSNA), and norepinephrine (NE) secretion from the posterior hypothalamic nuclei (PH), and reduces the abundance of interleukin-1ß (IL-1ß) and neuronal NO synthase (nNOS) mRNA in the PH. Pretreatment with an Ang II type 1 (AT₁) receptor antagonist abolished these effects of Ang II. The data support the hypothesis that Ang II stimulates SNS through activation of AT₁ receptors and downregulation of nNOS. In the current studies, we tested the hypothesis that the effects of Ang II on central SNS are mediated by reactive oxygen species. To this end, we evaluated the effects of Ang II alone or in combination with 2 superoxide dismutase (SOD) mimetics, tempol (4-hydroxy-2,2,6,6-tetramethyl piperidinoxyl) and polyethylene glycol–SOD (PEG-SOD) on BP, NE secretion from the PH, RSNA, and abundance of IL-1ß and nNOS mRNA in the PH Ang II raised BP, NE secretion from the PH, and RSNA and reduced the abundance of IL-1ß and nNOS mRNA in the PH. Tempol and PEG-SOD completely abolished these actions of Ang II. In conclusion, these studies support the hypothesis that the effects of centrally administered Ang II on the SNS are mediated by increased oxidative stress in brain regions involved in the noradrenergic control of BP.

Key Words: angiotensin II • sympathetic nerve activity • nitric oxide • interleukins

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