Impact of regular physical activity on the NAD(P)H oxidase and angiotensin receptor system in patients with coronary artery disease.
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.


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.
Adams
Volker
V
University Leipzig, Heart Center Leipzig, Department of Cardiology, Leipzig, Germany.
Linke
Axel
A
Kränkel
Nicolle
N
Erbs
Sandra
S
Gielen
Stephan
S
Möbius-Winkler
Sven
S
Gummert
Jan F
JF
Mohr
Friedrich Wilhelm
FW
Schuler
Gerhard
G
Hambrecht
Rainer
R
D000368:Aged; D000804:Angiotensin II / Q000494:pharmacology; D003324:Coronary Artery Disease / Q000201:enzymology / Q000378:metabolism* / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000503:physiopathology; D015444:Exercise; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism*; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism; D014661:Vasoconstriction; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation
D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D014662:Vasoconstrictor Agents; D013481:Superoxides; D000804:Angiotensin II; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases