Circulation Research. 2004;95:210-216
Published online before print June 10, 2004, doi: 10.1161/01.RES.0000135483.12297.e4
Published online before print June 10, 2004, doi: 10.1161/01.RES.0000135483.12297.e4
© 2004 American Heart Association, Inc.
Integrative Physiology |
Hypertension Caused by Angiotensin II Infusion Involves Increased Superoxide Production in the Central Nervous System
From the Department of Anatomy and Cell Biology (M.C.Z., E.L., R.V.S., R.L.D.), Free Radical and Radiation Biology Program, Department of Radiation Oncology (M.C.Z., R.L.D.), and The Cardiovascular Center (R.V.S., R.L.D.), The University of Iowa, Roy J. and Lucille A. Carver College of Medicine, Iowa City.
Correspondence to Robin L. Davisson, PhD, Department of Anatomy and Cell Biology, 1-251 Bowen Science Building, The University of Iowa College of Medicine, Iowa City, IA 52242. E-mail robin-davisson{at}uiowa.edu
Hypertension caused by angiotensin II (Ang II) infusion is associated with oxidative stress in the peripheral vasculature and kidney. The role of redox mechanisms in the central nervous system (CNS), a tissue known to be pivotal in Ang II–dependent hypertension, has not been investigated. We recently identified superoxide (O2·–) in the brain as a key signaling intermediate in the transient pressor response elicited by acute injection of Ang II directly into the CNS. Here we tested the hypothesis that hypertension caused by chronic systemic infusion of Ang II is mediated by a central neurogenic mechanism involving O2·–. Infusion of Ang II (600 ng · kg–1 · min–1) over a 2-week period in mice caused a gradually developing hypertension that was correlated with marked elevations in O2·– production specifically in the subfornical organ (SFO), a brain region lying outside the blood–brain barrier and known to be a primary sensor for blood-borne Ang II. Adenoviral-mediated delivery of cytoplasmically targeted superoxide dismutase (SOD) selectively to this site prevented the hypertension and the increased O2·– production, whereas gene transfer of SOD targeted to the extracellular matrix had no effect. These data suggest that increased intracellular O2·– production in the SFO is critical in the development of Ang II–induced hypertension.
Key Words: reactive oxygen species • brain • subfornical organ • neurons • blood pressure
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