Circulation Research. 2001;89:114-116
Published online before print July 5, 2001, doi: 10.1161/hh1401.094367
Published online before print July 5, 2001, doi: 10.1161/hh1401.094367
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© 2001 American Heart Association, Inc.
Reports |
Redox Signaling of the Arteriolar Myogenic Response
From the Heart and Lung Research Institute (P.T.N., S.F., H.H., S.M., N.A.F.), Ohio State University, Columbus, Ohio; National Institute of Allergy and Infectious Diseases (S.H.), Bethesda, Md; and Duke University (P.J.G.-C.), Durham, NC.
Correspondence to N.A. Flavahan, PhD, Heart and Lung Research Institute, 473 West 12th Ave, Room 110E, Columbus, OH 43210. E-mail flavahan-1{at}medctr.osu.edu
Abstract
Arteriolar vascular smooth muscle cells (VSMCs) are mechanosensitive, constricting to elevations in transmural pressure (PTM). The goal of the present study was to determine using mouse isolated tail arterioles and arteries whether oxidant signaling regulates this myogenic response. In response to PTM elevation, VSMCs of arterioles but not arteries generated constriction and increased reactive oxygen species (ROS) activity (using the H2O2-sensitive probe dichlorodihydrofluorescein). Arterioles had increased expression of NADPH oxidase components compared with arteries. Inhibition of NADPH oxidase, using mice with targeted impairment of enzyme components (p47phox or rac1) or diphenyleneiodonium, prevented the pressure-induced generation of ROS. When ROS activity was inhibited, either by inhibiting NADPH oxidase or with N-acetylcysteine, the myogenic constriction was abolished. The myogenic constriction was also inhibited by catalase, which inactivates H2O2, but was unaffected by a cell-permeant mimic of superoxide dismutase (MnTMPyP). 
1-Adrenergic constriction was not associated with altered ROS activity and was not affected by inhibition of NADPH oxidase or ROS. Exogenous H2O2 constricted VSMCs of arterioles but not arteries. Thus, NADPH oxidase and ROS, in particular H2O2, contribute to the myogenic response of arteriolar VSMCs.
Key Words: H2O2 • smooth muscle • pressure
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