title: Direct versus reflex activation of cardiac beta-adrenoceptors in the chronotropic and inotropic effects of isoprenaline and prenalterol in the conscious dog.
abstract: 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.(ABSTRACT TRUNCATED AT 250 WORDS)
mesh_terms: D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D001286:Atropine Derivatives / Q000494:pharmacology; D004285:Dogs; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000494:pharmacology; D007545:Isoproterenol / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D010276:Parasympatholytics / Q000494:pharmacology; D011294:Prenalterol / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*
chemical_list: D001286:Atropine Derivatives; D006584:Hexamethonium Compounds; D010276:Parasympatholytics; D011943:Receptors, Adrenergic, beta; D018738:Hexamethonium; D001262:Atenolol; C006649:methylatropine; D007545:Isoproterenol; D011294:Prenalterol