The Selectivity of Beta-adrenoceptor Antagonists on Cardiovascular and Bronchodilator Responses to Isoprenaline in the Anaesthetized Dog

1 The actions of five beta-adrenoceptor antagonists, chosen because of reported differences in their selectivities, were compared using the positive chronotropic, vasodepressor and bronchodilator responses to isoprenaline in anesthetized dogs. 2 Propranolol was a potent antagonist of the isoprenaline responses in all three systems. 3 Practolol and acebutolol (M & B 17,803) blocked the positive chronotropic responses to isoprenaline to a greater extent than the vasodepressor or bronchodilator responses. 4 Butoxamine and alpha-methyl dichloroisoprenaline showed the opposite selectivity, blocking the vasodepressor and bronchodilator responses to isoprenaline to a greater extent than positive chronotropic responses. However, both drugs were considerably less potent than the other antagonists studied and their selectivities were less clear-cut than those of practolol or acebutolol. 5 All the antagonists lowered the resting heart rate and to a lesser extent the diastolic blood pressure. The effects of propranolol, practolol and acebutolol on heart rate probably result from cardiac beta-adrenoceptor blockade. With butoxamine and alpha-methyl dichloro isoprenaline, however, the effects on heart rate probably result from a direct cardiodepressant action. 6 The relevance of the results to the problem of the sub-classification of beta-adrenoceptors is discussed.