RATE, FORCE AND CYCLIC ADENOSINE 3′, 5′-MONOPHOSPHATE RESPONSES TO (-)-ADRENALINE IN NEONATAL RAT HEART TISSUE

Abstract

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 ED50 values and maximal responses together with sensitivity to propranolol (pA2 values). 3 Resting force, corrected for sample size, did not change with age, whereas resting atrial rate doubled between 1 and 20 days. 4 ED50 concentrations in atria were constant with age, but decreased in ventricles. Cocaine (10−5 m) and other drugs did not consistently affect ED50 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 pA2 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 β-receptors. In 1 to 5 day-old ventricles, normal ED50 concentrations and good cyclic AMP response in the presence of a much reduced force response may indicate receptor-response transduction inefficiency, assuming a β1-receptor occupation and cyclic AMP production response mechanism for inotropism with adrenaline.