POSITIVE CHRONOTROPIC AND INOTROPIC RESPONSES TO BRL-37344, A BETA-3-ADRENOCEPTOR AGONIST IN ISOLATED, BLOOD-PERFUSED DOG ATRIA

We investigated the chronotropic and inotropic responses to BRL 37344 (a beta3-adrenoceptor agonist) and isoproterenol in isolated, blood-perfused dog atria. BRL 37344 (0.1-30 nmol) or isoproterenol (0.001-0.3 nmol) increased the sinus rate and contractile force dose dependently. BRL 37344 was 290 times less potent than isoproterenol to increase sinus rate and 140 times less potent to increase atrial force. Both propranolol and bisoprolol similarly inhibited the positive chronotropic and inotropic responses to BRL 37344 and isoproterenol dose dependently. ICI 118,551 (0.1 and 1 nmol) did not significantly affect the positive cardiac responses to BRL 37344 or isoproterenol. Neither imipramine nor tetrodotoxin significantly affected the positive cardiac responses to BRL 37344. These results suggest that the positive chronotropic and inotropic responses to BRL 37344 are mediated mainly by beta1-adrenoceptors in the dog heart. It is unlikely that beta3-adrenoceptors, as previously reported in adipose tissue or gastrointestinal smooth muscle, mediate chronotropic and inotropic responses in the normal dog heart.