1 The percentage of lignocaine free in the plasma of ten females receiving oral contraceptive medication was significantly greater than in 17 males of similar age (18-42 years). 2 In the same subjects the percentage of diazepam free in plasma was significantly greater in the contraceptive treated group than in 11 contraceptive-free females and significantly greater in contraceptive-free females than in males.3 The differences in lignocaine binding were almost completely attributable to changes in a,-acid glycoprotein concentration, which is reduced by oestrogens. The binding of diazepam was significantly related to albumin, a,-acid glycoprotein and non-esterified fatty acid concentrations which together were related to 55% of the variation in the binding of this basic compound.

SUMMARY The respective contributions of 3-adrenoceptor subtypes to the hemodynamic, humoral and metabolic consequences of adrenergic stimulation during graded exercise in man were investigated using nonselective 8-adrenoceptor blockade with propranolol and ,81-adrenoceptor blockade with atenolol. Doses of these agents that produced comparable suppression of 1,1 response as measured by antagonism of cardioacceleration during exercise were selected. Six healthy, nonsmoking males received these drugs in a placebo-controlled, Latin-square, randomized manner using a double-blind protocol. Both drugs produced comparable reductions of systolic blood pressure and elevation of diastolic blood pressure compared with placebo as exercise load increased. Propranolol produced higher peak epinephrine levels than atenolol or placebo (808 + 162, 640 190 and 584 153 pg/ml, respectively, p = 0.03), but norepinephrine levels did not show significant differences. Plasma renin activity was similarly suppressed both at rest and during all grades of exercise by both drugs. Lactate levels during moderate exercise were significantly lower after propranolol than after either atenolol or placebo (p = 0.03), but were similar at heavy work loads. Plasma glucose values rose on placebo (from 96.5 ± 2.1 to 97.7 2.7 mg/di) and on atenolol (from 99.7 ± 2.2 to 102.1 ± 4.8 mg/dl), but fell on propranolol (from 96.4 1.9 mg/dl to 87.2 ± 2.5 mg/dl, p < 0.01). These results indicate that blockade of vascular smooth muscle 12 receptors does not substantially alter hemodynamics during intense short-term exercise. Stimulation of renin release and lipolysis are produced through /83-adrenoceptor mechanisms, whereas /2 adrenoceptors are important in the provision of carbohydrate as an energy substrate for exercising muscle.

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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 of the hemodynamic and metabolic responses to acute exercise 2 h after prolonged prior exercise to induce skeletal muscle glycogen depletion, enhancing the dependence on hepatic glucose output and circulating free fatty acids (FFA). Plasma catecholamines were higher during exercise after, as opposed to before, glycogen depletion and were elevated further by all three drugs. Propranolol failed to produce a significant reduction in systolic blood pressure and elevated diastolic blood pressure. Atenolol reduced systolic blood pressure and did not change diastolic blood pressure. Both beta-blockers reduced FFA levels, but only propranolol lowered plasma glucose relative to placebo during exercise after glycogen depletion. In contrast, prazosin reduced systolic and diastolic blood pressures and resulted in elevated FFA and glucose levels. The results indicate important differences in the hemodynamic effects of beta 1-selective vs. nonselective beta-blockade during exercise after skeletal muscle glycogen depletion. Furthermore they confirm the importance of beta 2-mediated hepatic glucose production in maintaining plasma glucose levels during exercise. Acute alpha 1-blockade with prazosin induces reflex elevation of catecholamines, which in the absence of blockade of hepatic beta 2-receptors produces elevation of plasma glucose. The results suggest there is little role for alpha 1-mediated hepatic glucose production during exercise in humans.

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