Vascular effects of exercise training and lipid-lowering therapy at rest and during exercise in hypercholesterolaemia

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The health of the cells which line blood vessels, endothelial cells, is now known to be important in maintaining normal function of the circulation. In patients with elevated blood cholesterol concentration, the function of these cells is abnormal and this is considered to contribute importantly to the blood vessel dysfunction and cardiovascular disease seen in this condition. We have recently demonstrated that drug therapy aimed at decreasing cholesterol concentration in the blood can significantly improve blood vessel function. In other studies we have demonstrated that exercise training improves blood vessel function. The purpose of this research is to determine whether high blood cholesterol impairs exercise capacity by limiting blood flow to exercising muscle. It is also our goal to determine whether exercise training can produce benefit additional to that resulting from lowering cholesterol in those with initially high cholesterol. Blood vessel function will be studied at rest, in response to pharmacological stimulation and during exercise. Vascular function in the forearm will be assessed using synchronised ultrasound (high frequency sound, sonar) and Doppler measures which assess the size of, and flow in, the large artery near the elbow crease. During measurements, procedures are undertaken to alter flow in the arm blood vessels, some depending upon functional ability of the endothelial cells and some independent of those cells. In addition to assessment of blood vessel function, measurements of exercise tolerance will be taken before and after each intervention. By examining the effects of lipid-lowering and exercise training on rest and exercise blood flow responses, this research will help determine the best approach to improving blood vessel function and cardiovascular fitness in patients with high cholesterol.