doi: 10.1161/01.CIR.0000154560.88933.7E
(Circulation. 2005;111:555-562.)
© 2005 American Heart Association, Inc.
Coronary Heart Disease |
Impact of Regular Physical Activity on the NAD(P)H Oxidase and Angiotensin Receptor System in Patients With Coronary Artery Disease
From University Leipzig, Heart Center Leipzig, Departments of Cardiology (V.A., A.L., N.K., S.E., S.G., S.M.-W., G.S., R.H.) and Cardiac Surgery (J.F.G., F.W.M.), Leipzig, Germany.
Correspondence to Rainer Hambrecht, Professor of Medicine, Universität Leipzig, Herzzentrum, Klinik für Innere Medizin/Kardiologie, Strümpellstr 39, D-04289 Leipzig, Germany. E-mail hamr{at}medizin.uni-leipzig.de
Received August 12, 2004; revision received November 4, 2004; accepted November 10, 2004.
Background— In patients with stable coronary artery disease, physical exercise training (ET) improves endothelial dysfunction. A potential mechanism mediating the enhanced vasomotor function is a reduced breakdown of endothelium-derived nitric oxide by reactive oxygen species (ROS). The aim of the present study was to analyze the impact of ET on sources of ROS generation in the left internal mammary artery of patients with symptomatic coronary artery disease.
Methods and Results— In left internal mammary artery rings sampled during bypass surgery from 45 patients randomized to either a training (n=22) or an inactive control (n=23) group, the mRNA expression of NAD(P)H oxidase subunits, NAD(P)H oxidase activity, and ROS production were assessed. In addition, endothelial function, expression of angiotensin II (Ang II) receptor type 1 and 2 (AT1-R and AT2-R), and Ang II-mediated vasoconstriction were determined. ET resulted in a significant lower expression of gp91phox (23.1±0.5 versus 69.1±18.1 arbitrary units, training versus control), p22phox (0.7±0.3 versus 2.0±0.5 arbitrary units), and Nox4 (2.7±1.2 versus 5.4±1.0 arbitrary units). Enzymatic activity (2.1±0.3 versus 4.9±0.4 mU/mg) and ROS generation (0.02±0.01 versus 0.06±0.02 arbitrary units) were significantly lower in the training compared with the control group. On a functional level, ET resulted in improved acetylcholine-mediated vasodilatation and a 49% reduction in Ang II–induced vasoconstriction, accompanied by lower AT1-R (3.7±0.8 versus 16.6±5.7 arbitrary units, training versus control) and higher AT2-R (7.8±2.5 versus 1.6±0.7 arbitrary units) mRNA expression.
Conclusions— ET reduces vascular expression of NAD(P)H oxidase and AT1-R, resulting in decreased local ROS generation. These molecular effects converge in a reduced Ang II–mediated vasoconstriction.
Key Words: angiotensin • endothelium • exercise • polymerase chain reaction • vessels
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