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

We determined the relationship between the β₁- and β₂-adrenergic receptor subtypes in isolated myocytes and their physiological responsiveness in chronically instrumented conscious baboons and rats. In conscious baboons, isoproterenol (ISO) (0.02 μg/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 β₁-adrenergic receptor blockade, indicating that the predominant physiological response was mediated by β₁-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 by ISO were not different before and after β₁-blockade, indicating that β₂-adrenergic receptors were not blocked. In conscious rats, ISO (0.4 μg/kg) increased LV dP/dt by 50 ± 4.9% from 13252 ± 2002 mmHg/s and only by 10 ± 3.9% from 10793 ± 1364 mmHg/s after β₁-adrenergic receptor blockade; whereas decreases in mean arterial pressure induced by ISO were not different before and after β₁ 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 ¹²⁵I-cyanopindolol (¹²⁵I-cyp) and the subtype β₁-selective antagonist betaxolol and the β₁-selective antagonist ICI 118,551 indicated that the β₁/β₂ 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 β₁-adrenergic receptor mediated, which is consistent with the β₁/β₂ ratio in rat myocytes but not in baboon myocytes, where a significant fraction of β₂-adrenergic receptors does not appear to exert an effect on conctractility in vivo.