Direct versus reflex activation of cardiac beta-adrenoceptors in the chronotropic and inotropic effects of isoprenaline and prenalterol in the conscious dog.
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)
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*
D001286:Atropine Derivatives; D006584:Hexamethonium Compounds; D010276:Parasympatholytics; D011943:Receptors, Adrenergic, beta; D018738:Hexamethonium; D001262:Atenolol; C006649:methylatropine; D007545:Isoproterenol; D011294:Prenalterol