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Basic science: Cardiovascular disease basic research
e0016 Tongxinluo reduces myocardial ischaemia-reperfusion injury and no-reflow by stimulating the expression and phosphorylation of eNOS via PKA pathway
  1. Xiangdong Li1,
  2. Yuejin Yang1,
  3. Yong-Jian Geng2,
  4. Chen Jin1,
  5. Feng-Huan Hu1,
  6. Jing-Lin Zhao1,
  7. Hai-Tao Zhang1,
  8. Yu-Tong Cheng3,
  9. Hai-Yan Qian1,
  10. Lin-Lin Wang1,
  11. Bao-Jie Zhang1,
  12. Yi-Ling Wu4
  1. 1Fuwai Hospital And Cardiovascular Institute
  2. 2The University of Texas Houston Medical School
  3. 3Beijing An Zhen Hospital
  4. 4The Integration of Traditional And Western Medical Research Academy of Hebei Province

Abstract

Objective To investigate whether oral administration of Tongxinluo (TXL), a traditional Chinese medicine, at a single low loading dose 1 h before myocardial ischaemia can attenuate ischaemia-reperfusion injury by regulating endothelial nitric oxide synthase (eNOS) via protein kinase A (PKA) pathway.

Methods and results In 90-min ischaemia and 3-h reperfusion model, Minipigs were randomly assigned to four groups (n=8 in each group): (1) Sham; (2) Control; (3) TXL: 0.05 g·kg−1 of TXL was gavaged 1 h prior myocardial ischaemia; (4) TXL+H-89 (1.0 μg·kg−1·min−1, an inhibitor of PKA). TXL significantly decreased creatine kinase (CK) activity, reduced the infarct size from 78.5% to 59.2% and no-reflow area from 48.6% to 9.5% (p<0.05), while H-89 completely abolished the reduction of CK activity and necrosis size, and partially diminished the reduction of no-reflow size. TXL enhanced the PKA activity in ischaemic myocardium, increased the expression of PKA, Thr 198 p-PKA and Ser 635 p-eNOS in no-reflow area, and upregulated the expression of eNOS and Ser 1179 p-eNOS in reflow area. H-89 repressed the enhancement of PKA activity and the upregulation of eNOS and Ser 635 p-eNOS, but without great inhibition on the expression of PKA and Thr 198 p-PKA in no-reflow area, and even stimulated the expression of Ser 635 p-eNOS in reflow area.

Conclusion Pretreatment with single low loading dose of TXL 1 h before myocardial ischaemia reduces myocardial no-reflow and ischaemia-reperfusion injury by upregulating the expression of eNOS and p-eNOS (Ser 1179 and Ser 635), and this effect is partially mediated by PKA pathway.

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