Angiotensin (1-7) and Apelin co-therapy: New strategy for heart failure treatment of rats.

Objective: Isoproterenol (ISO)-induced heart failure is a standardized model for the study of beneficial effects of various drugs. Both apelin and angiotensin 1-7 have a cardiac protective effect. We assumed that co-therapy with apelin and angiotensin 1-7 [Ang (1-7)] may have synergistic cardioprotective effects against isoproterenol-induced heart failure. Methods: The rats were randomly assigned to one of eight groups, 7 animals in each, as follows: (1) Control I (saline; IP injection), (2) Control II (saline; via mini-osmotic pump), (3) ISO (5 mg/kg; IP), (4) Apelin (20 mu g/kg; IP), (5) Ang (1-7) (30 mu g/kg/day; via mini-osmotic pump), (6) Apelin+ISO, (7) Ang (1-7)+ISO, and (8) Apelin+Ang (1-7)+ISO. Rat myocardial injury was induced by intraperitonea I injection of 5 mg/kg of ISO for 10 days. Apelin and Ang (1-7) were administered 30 minutes before the ISO injection. Results: A decrease in the systolic blood pressure [SBP (p<0.001)], diastolic blood pressure [DBP (p=0.024)], left ventricular systolic pressure [LVSP (p<0.001)], left ventricular contractility [dP/dt max. (p<0.001)], relaxation [dP/dt min. (p<0.001)], and an increase in left ventricular end-diastolic pressure [LVEDP, (p<0.001)] were observed in ISO-treated rats. Plasma LDH and myocardial and plasma MDA were higher in the ISO heart than in controls (p<0.001). Histopathological examination of the cardiac tissue showed myocardial fibrosis and leukocyte infiltration in ISO-treated rats as compared to control. Co-therapy with apelin and Ang (1-7) was more effective than either agent used alone in restoring these parameters to that of control rats. Conclusion: The results of this study showed that the combination of apelin and Ang (1-7) had a more cardioprotective effect than either used alone against ISO-induced heart failure, and co-therapy may be a useful treatment option for myocardial injuries and heart failure.