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

Yanning Cui, You Tang Shen, Bernd Kalthof, Mitsunori Iwase, Naoki Sato, Masami Uechi, Stephen F. Vatner, Dorothy E. Vatner

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21 Scopus citations

Abstract

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 β12 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 β12 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.

Original languageEnglish (US)
Pages (from-to)1307-1317
Number of pages11
JournalJournal of Molecular and Cellular Cardiology
Volume28
Issue number6
DOIs
StatePublished - Jun 1996
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Keywords

  • Baboon
  • Contractility
  • Isolated myocytes
  • Rat
  • β-adrenergic receptor subtypes

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