Effects of physical exercise on coronary and peripheral vascular function. An integrative physiological study from rat to man

• Physical exercise is beneficial for the cardiovascular health. Numerous epidemiological studies reveal that physical activity reduces the risk of cardiovascular related death. Nevertheless, the underlying vessel wall specific physiological and molecular mechanisms still remain incompletely understood. The aim of this thesis was to investigate coronary and peripheral vascular function as a consequence of exercise and a physically active lifestyle. A wheel-cage model for voluntary running in spontaneously hypertensive rats was used to mimic the human exercise situation. Endothelial function in conduit and resistance arteries was investigated using myograph techniques. Vascular stiffness was studied in vivo, using tissue Doppler imaging, and ex vivo, using a perfusion chamber and ultrasound biomicroscopy. High-frequency echocardiography was used to assess cardiac function and coronary flow velocity reserve (CFVR) in the left anterior descending coronary artery. A broad-base gene expression microarray analysis of aortic tissue was performed, and gene expressions of endothelial nitric oxide synthase (eNOS), copper zinc superoxide dismutase (CuZnSOD) and heat shock proteins 60 and 70 (HSP60 and HSP70) were validated with real-time PCR. Young healthy adults were submitted to studies of flow-mediated vasodilation (FMD), intima-media thickness (IMT), arterial wall stiffness index (SI), echocardiographic examination, CFVR measurements and sub-maximal exercise capacity (VO2maxc). We found that CFVR, resistance artery endothelial function and aortic compliance are improved after exercise in rats. Microarray analysis revealed a concerted down-regulation of HSP genes. After training, aortic and cardiac CuZnSOD gene expression was upregulated, while eNOS remained unchanged. In man, VO2maxc was positively correlated to CFVR and negatively correlated to IMT and SI. FMD was increased in subjects with high compared to moderate VO2maxc. Subjects with high CFVR had high ratios between endothelial-dependent and independent vasodilation in the forearm and low SI. We conclude that a physically active life-style is beneficial for coronary and peripheral artery function in young adults. Aerobic exercise is responsible for the exercise-induced cardiovascular effects, which are independent of blood lipids, in a young population. Also, exercise-induced upregulation of antioxidative enzymes might be a key mechanism underlying peripheral and coronary artery function. HSP might play a role in exercise-induced beneficial vascular effects. Finally, the established methodological platform may facilitate translational physiological studies from animal to man.

Nyckelord

exercise

endothelial function

coronary flow velocity reserve

colour Doppler echocardiography

oxidative stress

gene expression

stiffness

ultrasound biomicroscopy

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