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). CONCLUSION: 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.
