Hemodynamic and metabolic responses to exercise after alpha 1-, beta 1-, and nonselective beta-adrenoceptor blockade in man.

The effects of acute alpha 1-adrenoceptor blockade with prazosin, beta 1-adrenoceptor blockade with atenolol, and nonselective beta-adrenoceptor blockade with propranolol were compared in a placebo-controlled crossover study. The study involved measurement of the hemodynamic and metabolic responses to exercise after heavy exercise in order to induce skeletal muscle glycogen depletion and thus enhance the dependence on hepatic glucose output and circulating free fatty acids. Catecholamine responses to exercise were enhanced by glycogen depletion and by both beta-blocking drugs. Catecholamine levels were highest with propranolol; as a consequence, at high work loads, propranolol failed to produce a significant reduction in systolic blood pressure and elevated diastolic blood pressure. At high work loads, atenolol reduced systolic blood pressure but did not change diastolic blood pressure. Both beta blockers reduced free fatty acid levels, but only propranolol accelerated the fall of plasma glucose levels during "glycogen-depleted" exercise. In contrast, during exercise prazosin reduced systolic and diastolic blood pressures, and elevated heart rate and plasma catecholamines, particularly noradrenaline. Concomitantly, prazosin raised free fatty acid and lactate levels, and increased the plasma glucose level at a time when placebo therapy resulted in a steady fall in glucose levels. The results indicate important differences in the hemodynamic effects of cardioselective versus nonselective beta-blockade during long-term (or glycogen-depleted) exercise. The importance of beta 2-mediated hepatic glycogenolysis in man is confirmed. Acute alpha 1-blockade with prazosin induces reflex elevation of catecholamine levels. There is no indication of an important role for an alpha 1-mediated mechanism in hepatic glucose production in man.

Duke Scholars

Author Robert Sanders Williams Medicine, Cardiology