Beta-2 adrenergic blockade evaluated with epinephrine after placebo, atenolol, and nadolol

Abstract

Vascular .beta.2-adrenergic blocking effects of the water-soluble drugs atenolol (.beta.1-selective) and nadolol (nonselective) were evaluated. Healthy young men (24) were studied in 3 dosing groups (8 subjects per group) before and after 1 wk on placebo, atenolol (50 mg twice a day), or nadolol (40 mg twice a day). Maximal treadmill exercise heart rates were reduced to a similar degree by atenolol (-48 .+-. 3 bpm) and nadolol (-48 .+-. 4 bpm) but were not affected by placebo. Trough blood levels were 226 .+-. 9 ng/ml for atenolol and 43 .+-. 9 ng/ml for nadolol. Calf blood flow was measured with a plethysmograph and calf vascular resistance was calculated from blood pressure and flow. .beta.2-Adrenergic blockade was determined at rest with epinephrine infused i.v. in graded doses from 0.001-0.032 .mu.g/kg/min. Mean arterial pressure and calf vascular resistance rose markedly after nadolol but not after atenolol or placebo. Marked bradycardia developed after nadolol, probably by baroreceptor stimulation. Thus at an equivalent, substantial degree of .beta.1-adrenergic blockade, nadolol blocks vascular .beta.2-adrenergic receptors and atenolol does not. Measurement of the peripheral vascular response to epinephrine infusion is an effective means of assessing the impact of .beta.-adrenergic blockers on vascular .beta.2-adrenergic receptors.