title: Observations on the mechanism underlying the differences in exercise and isoprenaline tachycardia after cardioselective and non-selective beta-adrenoceptor antagonists.
abstract: 1 Differences in ability to attenuate isoprenaline tachycardia between the cardioselective beta-adrenoceptor antagonist atenolol and the non-selective drug propranolol, when administered in equivalent anti-exercise tachycardia oral doses, were measured in four normal volunteers. 2 Propranolol at all dose comparisons showed a greater potency in antagonism of isoprenaline tachycardia than atenolol; this ranged from 6 at the lowest doses (40 and 50 mg respectively) to 13 at the highest doses (320 and 400 mg respectively). 3 After doses of each drug which produced equal inhibition of exercise tachycardia, isoprenaline induced a greater increase in heart rate and greater decrease in diastolic blood pressure after pre-treatment with atenolol than after propranolol. 4 The contribution of this isoprenaline induced vasodilatation to the reduced tachycardia response, 1 h after 25 mg oral atenolol, was measured in the same four subjects by correction of the hypotension with an intravenous angiotensin infusion. Reversal by angiotensin of the 17 mm Hg average fall in diastolic blood pressure during the sustained isoprenaline infusion did not reduce the tachycardia. 5 The hypotension that results from isoprenaline stimulation of unblocked vasodilator beta 2-adrenoceptors in normal subjects pre-treated with atenolol appears to make a negligible contribution to the tachycardia response and does not explain the different abilities of cardioselective and non-selective beta-adrenoceptor blocking drugs to antagonise isoprenaline tachycardia. Our results are compatible with the presence of beta 2-adrenoceptors in human atria.
mesh_terms: D000328:Adult; D001262:Atenolol / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007545:Isoproterenol / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D008297:Male; D008875:Middle Aged; D005082:Physical Exertion / Q000187:drug effects*; D011412:Propanolamines / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology*; D013610:Tachycardia / Q000139:chemically induced*
chemical_list: D011412:Propanolamines; D001262:Atenolol; D011433:Propranolol; D007545:Isoproterenol