title: Urotensin-ⅡReceptor Antagonist SB-710411 Protects Rat Heart against Ischemia-Reperfusion Injury via RhoA/ROCK Pathway.
abstract: OBJECTIVE
  SB-710411 is a rat selective urotensin-II (U-II) receptor antagonist, which can block U-II-induced contraction of the aorta and inhibit U-II-induced myocardial fibrosis in rats. However, the effect of SB-710411 on myocardial ischemia-reperfusion (I/R) injury is unclear. The present study was designed to investigate whether SB-710411 has a protective effect on myocardial I/R injury in rats and the possible mechanisms.
  
  
  RESULTS
  Myocardial I/R injury was induced by occluding the left anterior descending coronary artery in adult male Sprague-Dawley rats. Hemodynamic parameters, electrocardiogram (ECG), infarct size, histological alteration, lactate dehydrogenase (LDH), creatine phosphokinase-MB (CK-MB), cardiac troponin I (cTnI), RhoA, and the protein expressions of U-II receptor (UTR), ROCK1 and ROCK2 were evaluated. Cardiac I/R injury significantly up-regulated the expressions of UTR, ROCK1 and ROCK2 proteins in rat myocardium. SB-710411 1.0 and 2.0 μg/kg significantly reduced cardiac I/R-induced the infarct size and histological damage in rat myocardium, markedly inhibited the changes of hemodynamic parameters and the increases of ST-segment in ECG, the serum LDH and CK-MB activities and cTnI level in rats subjected to myocardial I/R injury. Furthermore, SB-710411 obviously prevented myocardial I/R-increased RhoA activity and UTR, ROCK1 and ROCK2 protein expressions.
  
  
  CONCLUSIONS
  Our results indicate that cardiac I/R injury increases myocardial UTR expression, and SB-710411 has a potent protective effect on myocardial I/R injury in rats. The cardioprotection may be associated with the inhibition of UTR-RhoA/ROCK pathway.
authors.affiliation: Department of Pharmacology, Anhui Medical University, Hefei, Anhui, China.|Anhui academy of medical sciences, Hefei, Anhui, China.
authors.forename: Sheng-Yong
authors.initials: SY
authors.lastname: Luo
authors.affiliation: Xinglin College of Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Biochemistry and Molecular Biology, Anhui Medical University, Hefei, Anhui, China.
authors.forename: Yi-De
authors.initials: YD
authors.lastname: Qin
authors.affiliation: Department of Pharmacology, Anhui Medical University, Hefei, Anhui, China.
authors.forename: Zhi-Wu
authors.initials: ZW
authors.lastname: Chen
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000627:therapeutic use; D006321:Heart / Q000187:drug effects; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D010456:Peptides, Cyclic / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014579:Urotensins / Q000037:antagonists & inhibitors; D054460:rho-Associated Kinases / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: D002316:Cardiotonic Agents; D010456:Peptides, Cyclic; C473646:SB-710411; D014579:Urotensins; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein