title: The inotropic effects of ammonia on isolated perfused rat hearts and the mechanisms involved.
abstract: Ammonia (NH(3)) 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 NH(3) in the nervous system have been studied. Recently, endogenous NH(3) has been suggested to be a gas transmitter. However, so far the role of NH(3) in cardiovascular functions has not been reported. The present study was designed to investigate the inotropic effects of NH(3) on isolated perfused rat hearts and the possible mechanisms involved in these effects. The results showed that NH(3) had a positive inotropic effect in a concentration-dependent manner and produced a higher positive effect than NaOH and NH(4)Cl. At low concentrations, the effect of NH(3) on cardiac function was caused by NH(3) molecules; at high concentrations, the effect of NH(3) on hearts may be partly correlated with a change of pH value, but was mainly caused by NH(3) molecules. The mechanisms involved in the NH(3)-induced positive inotropic effect may be related to the ATP-sensitive K(+) (K(ATP)) channel and the nitric oxide (NO)-cyclic GMP (cGMP) signaling pathway. In addition, at a concentration of 1.5 mmol l(-1), NH(3) 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 Ca(2+),Mg(2+)-ATPase in the hearts. These results indicate that NH(3) 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.
authors.affiliation: Institute of Environmental Medicine and Toxicology, Research Center of Environmental Science and Engineering, Shanxi University, Taiyuan 030006,  China.
authors.forename: Quanxi
authors.initials: Q
authors.lastname: Zhang
authors.forename: Ziqiang
authors.initials: Z
authors.lastname: Meng
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D000641:Ammonia / Q000494:pharmacology*; D000643:Ammonium Chloride / Q000494:pharmacology; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D003402:Creatine Kinase / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D006162:Guanylate Cyclase / Q000378:metabolism; D006321:Heart / Q000187:drug effects* / Q000502:physiology*; D006352:Heart Ventricles / Q000187:drug effects; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D066298:In Vitro Techniques; D054086:KATP Channels / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010069:Oxadiazoles / Q000494:pharmacology; D010078:Oxazines / Q000494:pharmacology; D010477:Perfusion; D011312:Pressure; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism; D012972:Sodium Hydroxide / Q000494:pharmacology; D012995:Solubility / Q000187:drug effects
chemical_list: D002316:Cardiotonic Agents; D054086:KATP Channels; C111257:NS 2028; D010069:Oxadiazoles; D010078:Oxazines; D051640:Small-Conductance Calcium-Activated Potassium Channels; D000643:Ammonium Chloride; D009569:Nitric Oxide; D012972:Sodium Hydroxide; D000641:Ammonia; D007770:L-Lactate Dehydrogenase; D019001:Nitric Oxide Synthase; D003402:Creatine Kinase; D000251:Adenosine Triphosphatases; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester