The inotropic effects of ammonia on isolated perfused rat hearts and the mechanisms involved

Abstract

SUMMARY Ammonia (NH3) is a common exogenous gas in the atmosphere, as well as an endogenous chemical produced by amino acid catabolism and other pathways in vivo. Physiological and pathophysiological roles of NH3 in the nervous system have been studied. Recently, endogenous NH3 has been suggested to be a gas transmitter. However, so far the role of NH3 in cardiovascular functions has not been reported. The present study was designed to investigate the inotropic effects of NH3 on isolated perfused rat hearts and the possible mechanisms involved in these effects. The results showed that NH3 had a positive inotropic effect in a concentration-dependent manner and produced a higher positive effect than NaOH and NH4Cl. At low concentrations, the effect of NH3 on cardiac function was caused by NH3 molecules; at high concentrations, the effect of NH3 on hearts may be partly correlated with a change of pH value, but was mainly caused by NH3 molecules. The mechanisms involved in the NH3-induced positive inotropic effect may be related to the ATP-sensitive K+ (KATP) channel and the nitric oxide (NO)–cyclic GMP (cGMP) signaling pathway. In addition, at a concentration of 1.5 mmol l–1, NH3 significantly increased the activity of creatine kinase (CK) and lactate dehydrogenase (LDH) in the coronary perfusate and decreased the activity of Na+,K+-ATPase and Ca2+,Mg2+-ATPase in the hearts. These results indicate that NH3 at physiological or low concentrations may play a modulatory role in heart function, but at high concentrations had a damaging effect on isolated rat hearts.