Rate, force and cyclic adenosine 3',5'-monophosphate responses to (--)-adrenaline in neonatal rat heart tissue

1 (-)-Adrenaline sensitivity in 1 to 20 day-old rat heart tissue was investigated as rate, force and cyclic adenosine 3',5'-monophosphate (cyclic AMP) production responses together with sensitivity to (+/-)-propranolol blockade.2 Resting performances were measured and responsiveness to (-)-adrenaline then determined as ED(50) values and maximal responses together with sensitivity to propranolol (pA(2) values).3 Resting force, corrected for sample size, did not change with age, whereas resting atrial rate doubled between 1 and 20 days.4 ED(50) concentrations in atria were constant with age, but decreased in ventricles. Cocaine (10(-5) M) and other drugs did not consistently affect ED(50) values.5 Maximal responses were not age-dependent in right atria, but increased in left atria. In 2 to 5 day-old hearts there was no inotropic response to adrenaline and the very small maximal response in ventricles rose 5 to 7 fold by 20 days.6 Propranolol sensitivity increased slightly (2 to 4 times) with age in all tissue from a pA(2) value of 7.5 at 2 days to 8.2 at 20 days.7 Control cyclic AMP was higher in 2 day than in 20 day-old tissue and in atria than ventricular strips or hearts. In 2 and 20 day-old atria, hearts and ventricles, force increases with different adrenaline concentrations correlated linearly with the log of the increase in cyclic AMP. Such a correlation was not seen in 2 day hearts and ventricles for cyclic AMP rose without corresponding force increases.8 Results suggest slight maturational changes in atrial beta-receptors. In 1 to 5 day-old ventricles, normal ED(50) concentrations and good cyclic AMP response in the presence of a much reduced force response may indicate receptor-response transduction inefficiency, assuming a beta(1)-receptor occupation and cyclic AMP production response mechanism for inotropism with adrenaline.