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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2002-4-17
pubmed:abstractText
1. We investigated the inhibitory effects of a non-acylguanidine Na(+)-H(+) exchange (NHE) inhibitor, T-162559 ((5E,7S)-[7-(5-fluoro-2-methylphenyl)-4-methyl-7,8-dihydro-5(6H)-quinolinylideneamino] guanidine dimethanesulphonate), on NHE-1, and its cardioprotective effect against ischaemia and reperfusion injury in rats and rabbits. 2. T-162559 inhibited human platelet NHE-1 in a concentration-dependent manner, with an IC(50) value of 13+/-3 nmol l(-1), making it 16 and three times more potent than cariporide IC(50): 209+/-75 nmol l(-1), P<0.01) and eniporide (IC(50): 40+/-11 nmol l(-1), P=0.066), respectively. T-162559 also inhibited rat NHE-1 with an IC(50) value of 14+/-2 nmol l(-1), which was five and three times lower than that of cariporide (IC(50): 75+/-7 nmol l(-1), P<0.01) and eniporide (IC(50): 44+/-2 nmol l(-1), P<0.01), respectively. 3. T-162559 inhibited, in a concentration-dependent manner, the reduction in cardiac contractility, progression of cardiac contracture, and increase in lactate dehydrogenase release after global ischaemia and reperfusion in perfused rat hearts. The inhibitory effects of T-162559 were observed at a lower concentration range (10 - 100 nmol l(-1)) than with cariporide and eniporide. T-162559 did not alter basal cardiac contractility or coronary flow after reperfusion, suggesting that it exerts direct cardioprotective effects on the heart. 4. Intravenous administration of T-162559 (0.03 and 0.1 mg kg(-1)) significantly inhibited the progression of myocardial infarction induced by left coronary artery occlusion and reperfusion in rabbits; the infarct size normalized by area at risk was 74+/-6% in the vehicle group, and 47+/-5% and 51+/-7% in the T-162559-0.03 mg kg(-1) and T-162559-0.1 mg kg(-1) groups (both P<0.05), respectively. 5. These results indicate that the new structural NHE-1 inhibitor T-162559 is more potent than cariporide and eniporide and possesses a cardioprotective effect against ischaemia and reperfusion injury in rat and rabbit models.
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/11959803-10226157, http://linkedlifedata.com/resource/pubmed/commentcorrection/11959803-10337448, http://linkedlifedata.com/resource/pubmed/commentcorrection/11959803-10422780, http://linkedlifedata.com/resource/pubmed/commentcorrection/11959803-10532945, http://linkedlifedata.com/resource/pubmed/commentcorrection/11959803-10598129, http://linkedlifedata.com/resource/pubmed/commentcorrection/11959803-10604890, http://linkedlifedata.com/resource/pubmed/commentcorrection/11959803-10980282, http://linkedlifedata.com/resource/pubmed/commentcorrection/11959803-11082127, http://linkedlifedata.com/resource/pubmed/commentcorrection/11959803-11120691, http://linkedlifedata.com/resource/pubmed/commentcorrection/11959803-11412833, http://linkedlifedata.com/resource/pubmed/commentcorrection/11959803-11518185, http://linkedlifedata.com/resource/pubmed/commentcorrection/11959803-1721542, http://linkedlifedata.com/resource/pubmed/commentcorrection/11959803-1851786, http://linkedlifedata.com/resource/pubmed/commentcorrection/11959803-2439517, http://linkedlifedata.com/resource/pubmed/commentcorrection/11959803-2551525, http://linkedlifedata.com/resource/pubmed/commentcorrection/11959803-2832967, http://linkedlifedata.com/resource/pubmed/commentcorrection/11959803-2843057, http://linkedlifedata.com/resource/pubmed/commentcorrection/11959803-2852254, http://linkedlifedata.com/resource/pubmed/commentcorrection/11959803-6323465, http://linkedlifedata.com/resource/pubmed/commentcorrection/11959803-7039345, http://linkedlifedata.com/resource/pubmed/commentcorrection/11959803-7736504, http://linkedlifedata.com/resource/pubmed/commentcorrection/11959803-7759094, http://linkedlifedata.com/resource/pubmed/commentcorrection/11959803-7760373, http://linkedlifedata.com/resource/pubmed/commentcorrection/11959803-7864067, http://linkedlifedata.com/resource/pubmed/commentcorrection/11959803-7900878, http://linkedlifedata.com/resource/pubmed/commentcorrection/11959803-8141358, http://linkedlifedata.com/resource/pubmed/commentcorrection/11959803-8205693, http://linkedlifedata.com/resource/pubmed/commentcorrection/11959803-8246907, http://linkedlifedata.com/resource/pubmed/commentcorrection/11959803-8476023, http://linkedlifedata.com/resource/pubmed/commentcorrection/11959803-8663100, http://linkedlifedata.com/resource/pubmed/commentcorrection/11959803-8831938, http://linkedlifedata.com/resource/pubmed/commentcorrection/11959803-8989647, http://linkedlifedata.com/resource/pubmed/commentcorrection/11959803-9016300, http://linkedlifedata.com/resource/pubmed/commentcorrection/11959803-9060913, http://linkedlifedata.com/resource/pubmed/commentcorrection/11959803-9396463, http://linkedlifedata.com/resource/pubmed/commentcorrection/11959803-9428974, http://linkedlifedata.com/resource/pubmed/commentcorrection/11959803-9473125, http://linkedlifedata.com/resource/pubmed/commentcorrection/11959803-9655858, http://linkedlifedata.com/resource/pubmed/commentcorrection/11959803-9774180
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0007-1188
pubmed:author
pubmed:issnType
Print
pubmed:volume
135
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1995-2003
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
In vitro and in vivo pharmacology of a structurally novel Na+-H+ exchange inhibitor, T-162559.
pubmed:affiliation
Pharmacology Research Laboratories I, Takeda Chemical Industries, LTD., Osaka 532-8686, Japan. kusumoto_keiji@takeda.co.jp
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