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Inflammopharmacology

, Volume 27, Issue 6, pp 1309–1318 | Cite as

Urotensin-#receptor antagonist SB-706375 protected isolated rat heart from ischaemia–reperfusion injury by attenuating myocardial necrosis via RhoA/ROCK/RIP3 signalling pathway

  • Jing-Si Duan
  • Shuo Chen
  • Xiao-Qing Sun
  • Juan DuEmail author
  • Zhi-Wu ChenEmail author
Original Article

Abstract

SB-706375 is a selective receptor antagonist of human urotensin-II (hU-II), which can block the aorta contraction induced by hU-II in rats. The effect of SB-706375 on myocardial ischaemia–reperfusion (I/R) injury is unclear. The major objective of this study was to investigate whether SB-706375 has a protective effect on myocardial I/R injury in rats and explore its possible mechanisms. Isolated hearts of Adult Sprague–Dawley were perfused in a Langendorff apparatus, and haemodynamic parameters, lactate dehydrogenase (LDH), creatine phosphokinase-MB (CK-MB), cardiac troponin I (cTnI), RhoA, and the protein expressions of U-II receptor (UTR), receptor-interacting protein 3 (RIP3), Rho-associated coiled-coil-containing protein kinase 1 (ROCK1) and Rho-associated coiled-coil-containing protein kinase 2 (ROCK2) were assessed. We found that SB-706375 (1 × 10−6 and 1 × 10−5 mol/L) significantly inhibited the changes of haemodynamic parameters and reduced LDH and CK-MB activities and also cTnI level in the coronary effluents in the heart subjected to myocardial I/R injury. Further experiments studies showed that SB-706375 obviously prevented myocardial I/R increased RhoA activity and UTR, RIP3, ROCK1, and ROCK2 protein expressions. ROCK inhibition abolished the improving effect of SB-706375 on myocardial I/R-induced haemodynamic change in the isolated perfused rat heart. These findings suggested that SB-706375 provides cardio-protection against I/R injury in isolated rats by blocking UTR-RhoA/ROCK-RIP3 pathway.

Keywords

SB-706375 Myocardial ischaemia reperfusion injury UTR-RhoA/ROCK-RIP3 pathway 

Notes

Acknowledgements

This work was financially supported by the National Natural Science Foundation of China (Project # 81374002, to Z.-W. Chen).

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of PharmacologyAnhui Medical UniversityHefeiChina
  2. 2.Department of PhysiologyAnhui Medical UniversityHefeiChina
  3. 3.Department of Cardiovascular SurgeryThe 1st Affiliated Hospital of Anhui Medical UniversityHefeiChina

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