Ligand-independent negative chronotropic responses of rat and mouse right atria to beta-adrenoceptor antagonists

Negative chronotropic effects of beta-adrenoceptor (beta AR) antagonists on right atria from reserpine-treated rats and mice were determined as a test of their inverse agonist activities. beta(2)AR antagonist ICI-118,551 and nonselective beta AR antagonists alprenolol, propranolol, and timolol produ ced negative chronotropic effects. In contrast, nonselective beta AR antago nists pindolol and nadolol as well as beta(1)AR-selective antagonists ateno lol, acebutolol, and metoprolol did not cause a significant decrease in atr ial rates. The neutral antagonist pindolol but not the inverse agonist alpr enolol inhibited the negative chronotropic activities of ICI-118,551. Isopr enaline, salbutamol, and noradrenaline produced positive chronotropic effec ts; the chronotropic effects of isoprenaline and salbutamol but not of nora drenaline were antagonized by ICI-118,551. It is concluded that both beta(1 )AR and beta(2)AR mediate positive chronotropic effects of catecholamines o n rat and mouse atria but only beta(2)AR are constitutively active.