beta-2 Adrenergic blockade evaluated with epinephrine after placebo, atenolol, and nadolol

• Published in: Clinical pharmacology and therapeutics Vol. 37; no. 1; p. 2
• Main Authors: Hiatt, W R, Wolfel, E E, Stoll, S, Nies, A S, Zerbe, G O, Brammell, H L, Horwitz, L D
• Format: Journal Article
• Language: English
• Published: United States 01-01-1985
• Subjects: Adrenergic beta-Antagonists - pharmacology; Adult; Atenolol - blood; Atenolol - pharmacology; Blood Pressure - drug effects; Clinical Trials as Topic; Double-Blind Method; Epinephrine - pharmacology; Heart Rate - drug effects; Humans; Leg - blood supply; Male; Nadolol; Propanolamines - blood; Propanolamines - pharmacology; Random Allocation; Vascular Resistance - drug effects
• ISSN: 0009-9236
• DOI: 10.1038/clpt.1985.2

Vascular beta 2-adrenergic blocking effects of the water-soluble drugs atenolol (beta 1-selective) and nadolol (nonselective) were evaluated. Twenty-four healthy young men were studied in three dosing groups (eight 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 intravenously in graded doses from 0.001 to 0.032 micrograms/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.