Identification and functional role of beta-adrenergic receptor subtypes in primate and rodent: In vivo versus isolated myocytes

We determined the relationship between the beta(1)- and beta(2)-adrenergic receptor subtypes in isolated myocytes and their physiological responsiveness in chronically instrumented conscious baboons and rats. In conscious baboons, isoproterenol (ISO) (0.02 mu g/kg) increased left ventricular (LV) dP/dt by 89 +/- 6.7% from 2898 +/- 370 mmHg/s and only by 13 +/- 3.3% from 2491 +/- 146 mmHg/s after beta(1)-adrenergic receptor blockade, indicating that the predominant physiological response was mediated by beta(1)-adrenergic receptors. Decreases in mean arterial pressure (-11 +/- 0.5 mmHg v -16 +/- 4.6 mmHg) and coronary vascular resistance (-3.1 +/- 0.4 v -3.6 +/- 0.4 mmHg/ml/min) induced ISO were not different before and after beta(1)-blockade, indicating that beta(2)-adrenergic receptors were not blocked. In conscious rats, ISO (0.4 mu g/kg) increased LV dP/dt by 50 +/- 4.9% from 13 252 +/- 2002 mmHg/s and only by 10 +/- 3.9% from 10 793 +/- 1364 mmHg/s after beta(1)-adrenergic receptor blockade; whereas decreases in mean arterial pressure induced by ISO were not different before and after beta(1) blockade (-19 +/- 2.4 mmHg v -16 +/- 2.2 mmHg), i.e. very consistent with the physiological responses in baboons. In vitro studies of isolated myocytes, using radioligand binding with I-125-cyanopindolol (I-125-cyp) and the subtype beta(1)-selective antagonist betaxolol and the beta(2)-selective antagonist ICI 118 551 indicated that the beta(1)/beta(2) ratio of rat myocytes was 92/8; whereas baboon myocytes were more equally distributed (59/41). Thus, in both species the preponderance of effects of ISO on ventricular function was beta(1)-adrenergic receptor mediated, which is consistent with the beta(1)/beta(2) ratio in rat myocytes but not in baboon myocytes, where a significant fraction of beta(2)-adrenergic receptors does not appear to exert an effect on conctractility in vivo. (C) 1996 Academic Press Limited