The effects of a peripherally selective alpha 2-adrenoceptor antagonist, MK-467, on the metabolic and cardiovascular response to exercise in healthy man.

1. A double-blind, placebo controlled study has been conducted to investigate the consequences of i.v. treatment with MK-467, a peripherally selective alpha 2-adrenoceptor antagonist in exercising healthy male subjects. In particular, the effects on blood pressure, heart rate, circulating catecholamines (noradrenaline (NA) and adrenaline (A)), insulin, glucose and free fatty acids (FFA) were determined. 2. Exercise produced increases in catecholamines, blood pressure and heart rate. FFA increased at the start of the exercise but then declined as exercise progressed. 3. MK-467 significantly increased NA, in a dose-dependent manner, before and during exercise without altering A. Blood pressure and heart rate were not affected by drug treatment. 4. The insulin and FFA response to exercise was significantly enhanced by MK-467 although glucose was unaltered by drug. 5. It is concluded that both pre- and post-junctional peripheral alpha 2-receptors play an important role in the metabolic response to exercise in man.