Vasomotor Tone in Healthy Volunteers During Exercise

Timothy B. Curry, M.D., Ph.D.

IRB #: 1562-04

The exact mechanisms governing vasodilation in exercising muscle are poorly understood. This series of studies is intended to further elucidate the mechanisms of vasodilation in muscle during exercise and to test the hypothesis that ATP causes release of nitric oxide and vasodilation during exercise. Additionally we will explore the role of cGMP as a mediator of exercise hyperemia and functional sympatholysis (i.e., blunted sympathetic vasoconstriction in metabolically dilated tissues). Human subjects performing rhythmic handgrip exercise will be studied and drugs will be locally infused into the brachial artery to pharmacodissect the responses of interest. Drugs used to study nitric oxide­dependent vasodilation will be administered, including L­NMMA, methylene blue, and sildenafil. ATP will be administered along with these drugs to gain insight into the role of ATP and cGMP in exercise hyperemia and functional sympatholysis. It is expected that evidence supporting a key role for ATP as a mediator of exercise hyperemia and functional sympatholysis will be demonstrated and that ATP will act via the cGMP pathway.