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 animals were randomly assigned to one of eight groups of seven animals in each group as follows: (1) control I (saline; IP injection) (1) control II (saline; via mini-osmotic pump) (3) ISO (5 mg/ kg; IP), (4) Apelin (20μg/ kg; IP), (5) Ang (1-7) (30 μg/kg/day; via mini-osmotic pump), (6) Apelin+ISO, (7) Ang (1-7)+ISO, (8) Apelin+Ang (1-7)+ISO. Rat myocardial injury was induced by intraperitoneal injection of 5mg/kg of ISO for ten days. Apelin and Ang (1-7) were administered 30 minutes before ISO injection.

RESULTS

A decrease in systolic blood pressure (SBP; p<0.001), diastolic blood pressure (DBP; p<0.05), 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 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.