Cardioprotection of ramipril and BQ-123 against myocardial ischemia/reperfusion oxidative injury in vivo in rats / 中国药理学通报

ABSTRACT

Aim To investigate the protection of ramipril,BQ-123 and their combination against myocardial ischemia/reperfusion(I/R)injury in vivo in anesthetized rats,and to explore the mechanism of action of drugs on myocardial oxidation-antioxidation system.Methods Healthy male Wistar rats were divided into 5 groups randomly,sham operated(Sham)group,I/R group,ramipril(RAM)group,BQ-123(BQ)group and ramipril and BQ-123(R&B)group.All groups but not sham were subjected to I/R procedure.Twenty four hours before ligation,ramipril(1 mg·kg~(-1))was intragastrically administered to rats in RAM and R&B groups.The equal volume of normal saline was given to rats in other groups.BQ-123(10 μg·kg~(-1)· min-1)was infused intravenously from 10 min before ligation to the end of 30 min ischemia to rats in BQ and R&B groups.The equal volume of normal saline was given to other groups.HR,MAP and the change of ST-segment were observed;ventricular arrhythmias were monitored during ischemia;the infarct size was examined by TTC staining;the activity of myocardial T-SOD,Mn-SOD,CAT and the content of MDA were detected by spectrophotometer.Results Compared with I/R group,the elevation of ST-segment was decreased,onset of VPC and VT was delayed,duration of VPC and VT was shortened,incidence of VPC,VT and VF was decreased,IS and IS/AAR were improved,activity of T-SOD,Mn-SOD and CAT was increased,the content of MDA was decreased in RAM,BQ and R&B groups.Compared with RAM and BQ alone group,onset of VPC and VT,duration of VPC and VT,size,activity of T-SOD and Mn-SOD and content of MDA were changed dramatically in R&B group.Conclusions Ramipril,BQ-123 and the combined use of these two agents protected myocardium from I/R injury in vivo.The protective effects of the combination on delaying onset of VA,shortening duration of VA,decreasing infarct size and content of MDA,and increasing activity of SOD are better than those of using ramipril or BQ-123 alone.