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01-12-2019 | Verapamil | Original Article

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

Authors: Jing-Si Duan, Shuo Chen, Xiao-Qing Sun, Juan Du, Zhi-Wu Chen

Published in: Inflammopharmacology | Issue 6/2019

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.

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Title: Urotensin-#receptor antagonist SB-706375 protected isolated rat heart from ischaemia–reperfusion injury by attenuating myocardial necrosis via RhoA/ROCK/RIP3 signalling pathway
Authors: Jing-Si Duan
Shuo Chen
Xiao-Qing Sun
Juan Du
Zhi-Wu Chen
Publication date: 01-12-2019
Publisher: Springer International Publishing
Keyword: Verapamil
Published in: Inflammopharmacology / Issue 6/2019
Print ISSN: 0925-4692
Electronic ISSN: 1568-5608
DOI: https://doi.org/10.1007/s10787-019-00598-1

Keynote webinar | Spotlight on medication adherence

Springer Medicine

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

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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