title: [Effect of carvedilol and perindopril on Ca(2+) pump activity and Ca(2+)-release channel density in myocardial sarcoplasmic reticulum in rats with chronic heart failure following myocardial infarction].
abstract: OBJECTIVE
  To study the effects of carvedilol combined with perindopril on Ca(2+) pump activity and the density of Ca(2+)-release channel ryanodine receptor (RyR2) in the myocardial sarcoplasmic reticulum (SR) in rats with chronic heart failure caused by myocardial infarction.
  
  
  METHODS
  Rat models of chronic heart failure established by left coronary artery ligation were divided into different groups and treated with carvedilol (6 mg.kg(-1).d(-1)), perindopril (4 mg.kg(-1).d(-1)), terazosin (2 mg.kg(-1).d(-1)), or the combination of carvedilol (6 mg.kg(-1).d(-1)) and perindopril (4 mg.kg(-1).d(-1)) for 9 weeks. Another 12 rats with sham operation served as the sham-operated group. The hemodynamic parameters, activity of SR Ca(2+) pump, and RyR2 density were determined.
  
  
  RESULTS
  Compared with shame-operated group, the rats with chronic heart failure showed significantly increased left ventricular end-diastolic pressure (LVEDP) (P<0.01) and decreased +dP/dtmax, -dp/dtmax, activity of SR Ca(2+) pump and density of RyR2 (P<0.01). Both monotherapies with carvedilol and perindopril attenuated the increment of LVEDP, and significantly increased +dp/dtmax, -dp/dtmax, activity of SR Ca(2+) pump and density of RyR2 (P<0.01). Combined treatment even further enhanced the therapeutic effects, whereas terazosin produced no obvious effect. The activity of SR Ca(2+) pump was strongly correlated to +dp/dtmax and -dp/dtmax (r=0.596 and 0.684, respectively, P<0.01).
  
  
  CONCLUSIONS
  Prolonged treatment with beta-blocker carvedilol in combination with ACE inhibitor perindopril may improve the hemodynamic parameters, enhance Ca(2+) pump activity and increase the density of RyR2 of myocardial SR more effectively than either monotherapy in preventing and treating chronic heart failure following myocardial infarction.
authors.affiliation: Department of Cardiology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China. gengzhh@tom.com
authors.forename: Zhao-Hua
authors.initials: ZH
authors.lastname: Geng
authors.forename: Chun-Yan
authors.initials: CY
authors.lastname: Liu
authors.forename: You-Hua
authors.initials: YH
authors.lastname: Peng
authors.forename: Long-Gui
authors.initials: LG
authors.lastname: Li
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Zhao
authors.forename: Bin
authors.initials: B
authors.lastname: Cui
authors.forename: Shi-Yong
authors.initials: SY
authors.lastname: Yu
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002227:Carbazoles / Q000494:pharmacology* / Q000627:therapeutic use; D000077261:Carvedilol; D004359:Drug Therapy, Combination; D006333:Heart Failure / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D008297:Male; D009203:Myocardial Infarction / Q000150:complications / Q000378:metabolism; D020913:Perindopril / Q000494:pharmacology* / Q000627:therapeutic use; D011412:Propanolamines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D019837:Ryanodine Receptor Calcium Release Channel / Q000187:drug effects; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*
chemical_list: D002227:Carbazoles; D011412:Propanolamines; D019837:Ryanodine Receptor Calcium Release Channel; D000077261:Carvedilol; D002118:Calcium; D020913:Perindopril