Key result
Co-therapy with apelin and angiotensin (1-7) was more effective than either agent alone in restoring hemodynamic parameters and reducing myocardial injury in rats with ISO-induced heart failure.
Why the study?
Both apelin and angiotensin 1-7 have cardioprotective effects, prompting investigation into whether co-therapy confers synergistic cardioprotection against isoproterenol-induced heart failure.
Does co-therapy with apelin and angiotensin 1-7 improve hemodynamic and biochemical parameters in a rat model of isoproterenol-induced heart failure?
RCT (n=56)
Randomly assigned
Does co-therapy with apelin and angiotensin 1-7 improve hemodynamic and biochemical parameters in a rat model of isoproterenol-induced heart failure?
Co-therapy with apelin and angiotensin 1-7 provides synergistic cardioprotective effects in a rat model of isoproterenol-induced heart failure.
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.
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Ava Soltani Hekmat (2019) conducted an RCT in Isoproterenol (ISO)-induced heart failure (n=56). Apelin and Angiotensin (1-7) co-therapy vs. Isoproterenol alone, Apelin alone, Ang (1-7) alone, and saline controls was evaluated on Hemodynamic parameters, plasma LDH, myocardial and plasma MDA, and histopathological changes. Co-therapy with apelin and angiotensin (1-7) was more effective than either agent alone in restoring hemodynamic parameters and reducing myocardial injury in rats with ISO-induced heart failure.
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