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Direct versus reflex activation of cardiac beta-adrenoceptors in the chronotropic and inotropic effects of isoprenaline and prenalterol in the conscious dog

Direct versus reflex activation of cardiac beta-adrenoceptors in the chronotropic and inotropic effects of isoprenaline and prenalterol in the conscious dog

Journal de Pharmacologie 17(3): 266-274

The mechanisms by which isoprenaline and prenalterol increase heart rate and myocardial contractile force were investigated in conscious instrumented dogs. Isoprenaline (0.1 micrograms/kg/min/10 min) increased both heart rate (+98 +/- 14%) and contractility (+36 +/- 5%) and decreased diastolic blood pressure. beta 1-Adrenoceptor blockade abolished the isoprenaline induced increase in contractility whereas the induced tachycardia was reduced by approximately 50%. Either beta 2-blockade, which abolished the hypotensive effect of isoprenaline or ganglionic blockade, which abolished the isoprenaline-induced activation of sino aortic baroreflexes, strongly reduced (-67 +/- 8%) the isoprenaline-induced tachycardia but did not markedly alter the increase in contractility. However, the isoprenaline-induced increase in contractility was potentiated by methylatropine (+83 +/- 12%) whereas the simultaneous tachycardia was less marked than before methylatropine. In the same dogs, prenalterol (2 micrograms/kg/min/5 min) increased contractility (+38 +/- 5%) to the same extent as isoprenaline but induced a lesser increase in heart rate (+23 +/- 3%) and had no effect on aortic pressure. These effects were not significantly modified by pretreatments with either ganglionic or beta 2-blockades but were abolished by beta 1-blockade. After methylatropine the prenalterol-induced increase in heart rate was not modified but the increase in contractility was potentiated (+63 +/- 11%). We conclude that whereas indirect activation of arterial baroreflexes through hypotension markedly contributes to the isoprenaline-induced increase in heart rate, the simultaneous increase in cardiac inotropism is only dependent upon direct beta 1-adrenoceptor activation by isoprenaline.

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Accession: 039838606

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PMID: 2879069

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