Inverse agonist activities of beta-adrenoceptor antagonists in rat myocardium

1 Negative inotropic effects of several beta-adrenoceptor (beta AR) antagon ists on electrically-stimulated right atria, left atria, right ventricles a nd 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 anta gonist ICI-181,551 and nonselective beta AR antagonists alprenolol, nadolol , propranolol and timolol produced negative inotropic effects, which were m ost marked on the right atria. 3 The nonselective beta AR antagonist pindolol did not exhibit inverse agon ist activity but inhibited the negative inotropic activities of ICI-118,551 , atenolol and propranolol. 4 The negative inotropic effects of lidocaine, nifedipine and pentobarbiton e 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 is oprenaline. 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.