Exercise training and endothelial dysfunction in coronary artery disease and chronic heart failure. From molecular biology to clinical benefits.
Endothelial dysfunction (ED) has been documented in patients with both coronary artery disease (CAD) and chronic heart failure (CHF)-being responsible for exercise-induced myocardial ischemia in the former and increased afterload in the latter. In the last two decades exercise training has assumed a major role in both cardiovascular disorders. In CAD exercise training has established positive effects on myocardial perfusion. Recently, exercise training has been shown to attenuate paradoxical vasoconstriction in CAD. The improved ED after training explains the improvement of myocardial perfusion in the absence of changes in baseline coronary artery diameter. Since ED has been identified as a predictor of coronary events exercise may contribute to long-term reductions of cardiovascular mortality. In CHF the increased peripheral vascular resistance - especially during exercise - is more important. ED contributes to the peripheral vasoconstriction. Training programs have shown to improve ED in CHF. A long-term study of hemodynamic effects of training in CHF revealed a significant reduction of total peripheral resistance (TPR) that after 6 months with a concomitant increase in stroke volume. In a subgroup analysis a significant correlation between changes in TPR and changes in peripheral ED was observed. Cell culture and animal experiments suggest that shear stress increases the endothelial L-arginine uptake, enhances NO synthase activity and expression, and upregulates the production of extracellular superoxide dismutase, which prevents premature NO breakdown. All these molecular effects converge on a reduction of myocardial ischemic events in CAD and a decrease of afterload in CHF.
Gielen
S
S
University of Leipzig, Heart Center, Department of Internal Medicine, Cardiology, Leipzig, Germany.
Erbs
S
S
Schuler
G
G
Hambrecht
R
R
D002908:Chronic Disease; D003327:Coronary Disease / Q000201:enzymology / Q000503:physiopathology* / Q000517:prevention & control*; D004730:Endothelium, Vascular / Q000201:enzymology / Q000503:physiopathology*; D015444:Exercise; D006333:Heart Failure / Q000201:enzymology / Q000503:physiopathology* / Q000517:prevention & control*; D006439:Hemodynamics; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III
D009569:Nitric Oxide; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III