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Tetrandrine ameliorates ischaemia‐reperfusion injury of rat myocardium through inhibition of neutrophil priming and activation
Author(s) -
Shen YuhChiang,
Chen ChiehFu,
Sung YenJen
Publication year - 1999
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0702958
Subject(s) - tetrandrine , proinflammatory cytokine , reactive oxygen species , pharmacology , medicine , ischemia , downregulation and upregulation , chemistry , inflammation , biochemistry , gene
We have previously shown that tetrandrine (TTD), a bisbenzyltetrahydroiosquinoline isolated from the Chinese herb Stephania tetrandra , inhibits neutrophil adhesion, Mac‐1 expression, and reactive oxygen species (ROS) production. To examine whether inhibition of neutrophil function may confer upon TTD the ability to prevent myocardial ischaemia‐reperfusion (MI/R) injury, experiments were performed on rats subjected to coronary ligation followed by reperfusion for induction of MI/R injury. Intravenous administration of TTD (0.1 and 1.0 mg kg −1 ) 15 min prior to coronary ligation completely prevented MI/R‐associated mortality. TTD pretreatment also significantly reduced MI/R‐induced ventricular tachyarrhythmia, myocardial infarct size, and neutrophil infiltration. However, TTD pretreatment did not influence mean arterial blood pressure, heart rate, or product of pressure‐rate, indicating that TTD extenuated MI/R through mechanisms independent of modulating haemodynamics or myocardial oxygen demand. Peripheral blood neutrophils were isolated for ex vivo examination of shape change and Mac‐1 upregulation of neutrophils, two sensitive indicators of proinflammatory priming, as well as N ‐formyl‐methionyl‐leucyl‐phenylalanine (fMLP)‐induced adhesion and ROS production, parameters commonly used for the assessment of neutrophil activation. Neutrophils from MI/R animals showed significant shape change and Mac‐1 upregulation, both of which were prevented by TTD‐pretreatments. On the other hand, fMLP‐induced adhesion and ROS production of neutrophils were markedly enhanced by MI/R but diminished in TTD‐pretreated animals. These data suggest that the protective effect of TTD against MI/R injury can be accounted for by inhibition of neutrophil priming and activation, thereby abolishing subsequent infiltration and ROS production that cause MI/R injury.British Journal of Pharmacology (1999) 128 , 1593–1601; doi: 10.1038/sj.bjp.0702958