Inverse agonist activities of β-adrenoceptor antagonists in rat myocardium

1 Negative inotropic effects of several beta-adrenoceptor (beta AR) antagonists on electrically-stimulated right atria, left atria, right ventricles and left ventricular papillary muscles from reserpine-treated rats were used as a measure of their inverse agonist activities. 2 beta(1)AR antagonists acebutolol, atenolol and metoprolol, beta(2)AR antagonist ICI-181,551 and nonselective beta AR antagonists alprenolol, nadolol, propranolol and timolol produced negative inotropic effects, which were most marked on the right atria. 3 The nonselective beta AR antagonist pindolol did not exhibit inverse agonist activity but inhibited the negative inotropic activities of ICI-118,551, atenolol and propranolol. 4 The negative inotropic effects of lidocaine, nifedipine and pentobarbitone were similar on all the four myocardial preparations. 5 The positive inotropic efficacy of salbutamol on right and left atria but not on right ventricles and papillary muscles was comparable to that of isoprenaline. The antagonist activity of ICI-118,551 against isoprenaline was greater on right atria than on other cardiac regions. 6 beta(1)AR proteins were expressed in all regions of the heart but of beta(2)AR were primarily localized in the right atrium. 7 It is concluded that beta(2)AR play a greater role in right atria than in other cardiac regions and almost all beta AR antagonists behave as inverse agonists.