SELECTIVE BETA ADRENERGIC RECEPTOR ANTAGONISM IN THE ANESTHETIZED DOG

¹ Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, Texas

The beta adrenergic receptor blocking properties of practolol, butoxamine and propranolol on cardiac, vascular and bronchomotor responses to isoproterenol were determined in anesthetized dogs. The "pA₂" (in vivo equivalent of pA₂ value), the geometric mean ED50 values and the potency ratios were calculated from dose-response data for the effects of isoproterenol alone and after the administration of a range of doses of each antagonist. Although propranolol (0.03-1 mg/kg) exerted a relatively nonselective beta receptor blocking effect toward the cardiovascular and bronchiolar reresponses to isoproterenol, the "pA₂" values for propranolol for antagonizing the cardiac responses to isoproterenol (chronotropic 7.14; inotropic 7.26) differed from the vascular responses (arterial pressure, 7.58; perfusion pressure, 7.62). Practolol produced no significant antagonism of the vascular effects of isoproterenol in the dose range (0.1-3 mg/kg) which selectively antagonized its cardiac and pulmonary responses. Practolol was approximately one-third as potent as propranolol on cardiac and one-sixth as potent on bronchiolar responses. Butoxamine (1-10 mg/kg) selectively blocked the vascular and bronchiolar effects of isoproterenol, but had no significant effect on its cardiac responses. Butoxamine was approximately 1/100 as potent as propranolol on vascular responses and 1/50 as potent on bronchiolar responses. These results suggest that the cardiac, vascular and bronchiolar muscle in the dog each contains a different beta receptor subtype.