{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T03:30:33Z","timestamp":1769830233806,"version":"3.49.0"},"reference-count":40,"publisher":"The Company of Biologists","issue":"23","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,12,1]]},"abstract":"<jats:title>SUMMARY<\/jats:title><jats:p>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)\u2013cyclic GMP (cGMP) signaling pathway. In addition, at a concentration of 1.5 mmol l\u20131, 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.<\/jats:p>","DOI":"10.1242\/jeb.055947","type":"journal-article","created":{"date-parts":[[2011,11,9]],"date-time":"2011-11-09T18:19:55Z","timestamp":1320862795000},"page":"4048-4054","source":"Crossref","is-referenced-by-count":7,"title":["The inotropic effects of ammonia on isolated perfused rat hearts and the mechanisms involved"],"prefix":"10.1242","volume":"214","author":[{"given":"Quanxi","family":"Zhang","sequence":"first","affiliation":[{"name":"Institute of Environmental Medicine and Toxicology, Research Center of Environmental Science and Engineering, Shanxi University, Taiyuan 030006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ziqiang","family":"Meng","sequence":"additional","affiliation":[{"name":"Institute of Environmental Medicine and Toxicology, Research Center of Environmental Science and Engineering, Shanxi University, Taiyuan 030006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","reference":[{"key":"2021042506274399900_R1","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1038\/sj.bjp.0706906","article-title":"Regulation of vascular nitric oxide in vitro and in vivo: a new role for endogenous hydrogen sulphide?","volume":"149","author":"Ali","year":"2006","journal-title":"Br. J. Pharmacol."},{"key":"2021042506274399900_R2","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1111\/j.1748-1716.1981.tb06906.x","article-title":"Cerebrovascular effects of ammonia in vitro","volume":"113","author":"Andersson","year":"1981","journal-title":"Acta Physiol. Scand."},{"key":"2021042506274399900_R3","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/S0197-0186(99)00130-8","article-title":"Effect of ammonia on GABA uptake and release in cultured astrocytes","volume":"36","author":"Bender","year":"2000","journal-title":"Neurochem. Int."},{"key":"2021042506274399900_R4","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/0003-2697(76)90527-3","article-title":"A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding","volume":"72","author":"Bradford","year":"1976","journal-title":"Anal. Biochem."},{"key":"2021042506274399900_R5","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1023\/A:1021989230535","article-title":"Pathophysiology of hepatic encephalopathy: a new look at ammonia","volume":"17","author":"Butterworth","year":"2002","journal-title":"Metab. Brain Dis."},{"key":"2021042506274399900_R6","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1161\/01.RES.69.3.571","article-title":"ATP-regulated K+ channels protect the myocardium against ischemia\/reperfusion damage","volume":"69","author":"Cole","year":"1991","journal-title":"Circ. Res."},{"key":"2021042506274399900_R7","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/978-1-4615-2484-7_3","article-title":"Ammonia metabolism in mammals: interorgan relationships","volume":"341","author":"Cooper","year":"1994","journal-title":"Adv. Exp. Med. Biol."},{"key":"2021042506274399900_R8","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1111\/j.1939-1676.1994.tb03201.x","article-title":"Ammonia metabolism and the urea cycle: function and clinical implications","volume":"8","author":"Dimski","year":"1994","journal-title":"J. Vet. Intern. Med."},{"key":"2021042506274399900_R9","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1002\/(SICI)1097-4547(19961015)46:2<231::AID-JNR11>3.0.CO;2-5","article-title":"Ammonia-induced taurine release from cultured rabbit Muller cells is an osmoresistant process mediated by intracellular accumulation of cyclic AMP","volume":"46","author":"Faff","year":"1996","journal-title":"J. Neurosci. Res."},{"key":"2021042506274399900_R10","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/0006-8993(93)91157-N","article-title":"Effects of ammonium ions on synaptic transmission and on responses to quisqualate and N-methyl-D-aspartate in hippocampal CA1 pyramidal neurons in vitro","volume":"632","author":"Fan","year":"1993","journal-title":"Brain Res."},{"key":"2021042506274399900_R11","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1007\/BF00364459","article-title":"The influence of dietary manipulation on plasma ammonia accumulation during incremental exercise in man","volume":"63","author":"Greenhaff","year":"1991","journal-title":"Eur. J. Appl. Physiol. Occup. Physiol."},{"key":"2021042506274399900_R12","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1016\/S0891-5849(97)00134-2","article-title":"Decreased glutathione results in calcium-mediated cell death in PC12","volume":"23","author":"Jurma","year":"1997","journal-title":"Free Radic. Biol. Med."},{"key":"2021042506274399900_R13","doi-asserted-by":"crossref","first-page":"R1612","DOI":"10.1152\/ajpregu.00783.2004","article-title":"Glutamine-dependent inhibition of pial arteriolar dilation to acetylcholine with and without hyperammonemia in the rat","volume":"288","author":"Kawaguchi","year":"2005","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"2021042506274399900_R14","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/S0014-2999(97)01168-0","article-title":"Inhibition of nitric oxide synthase and soluble guanylate cyclase induces cardiodepressive effects in normal hearts","volume":"334","author":"Kojda","year":"1997","journal-title":"Eur. J. Pharmacol."},{"key":"2021042506274399900_R15","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/0301-0082(83)90012-6","article-title":"Ammonia metabolism in the CNS","volume":"20","author":"Kvamme","year":"1983","journal-title":"Prog. 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Pharmacol."},{"key":"2021042506274399900_R27","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1038\/sj.bjp.0706907","article-title":"What is the significance of vascular hydrogen sulphide (H2S)?","volume":"149","author":"O\u2019Sullivan","year":"2006","journal-title":"Br. J. Pharmacol."},{"key":"2021042506274399900_R28","doi-asserted-by":"crossref","first-page":"2241","DOI":"10.1172\/JCI107410","article-title":"Maximal rates of excretion and synthesis of urea in normal and cirrhotic subjects","volume":"52","author":"Rudman","year":"1973","journal-title":"J. Clin. Invest."},{"key":"2021042506274399900_R29","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/S0197-0186(02)00041-4","article-title":"Ammonia and Alzheimer\u2019s disease","volume":"41","author":"Seiler","year":"2002","journal-title":"Neurochem. 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Liver Physiol."},{"key":"2021042506274399900_R39","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.ejphar.2008.11.030","article-title":"The vasodilator mechanism of sulfur dioxide on isolated aortic rings of rats: involvement of the K+ and Ca2+ channels","volume":"602","author":"Zhang","year":"2009","journal-title":"Eur. J. Pharmacol."},{"key":"2021042506274399900_R40","article-title":"The negative inotropic effects of gaseous sulfur dioxide and its derivatives in the isolated perfused rat heart","author":"Zhang","year":"2010","journal-title":"Environ. 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