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.
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cardiology and Cardiovascular Medicine
- Isolated myocytes
- β-adrenergic receptor subtypes