Candoxatril combined losartan and omapatrilat decrease myocardial hypertrophy in rats
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Objective To compare the protective effect of candoxatril combined losartan on rat myocardial hypertrophy with omapatrilat (OMA) .Methods 1mg/kg isoproterenol (ISO) was given to induce myocardial hypertrophy in Sprague-Dawley (SD) rats. Rats were randomly divided into 7 groups: control, myocardial hypertrophy, candoxatril, losartan, OMA, candoxatril + losartan(full dose and half-value dose) （all n=8）. The myocardial hypertrophy index was expressed as heart weight /body weight (HW/BW),cross-sectional area (CSA), myocardial interstitial collagen volume fraction (CVF) and perivascular collagen area (PVCA); The content of plasma angiotensinⅡ(AngⅡ), atrial natriuretic peptide (ANP)and bradykinin (BK)were measured by colorimetry and radioimmunoassay;The expression of p-PI3K and p-Akt protein were detected by immunohistochemistry staining. Results 1) compared to control, ISO significantly increased heart weight index（3.64±0.30, 3.62±0.28, 4.32±0.58 respectively）, CSA, CVF, PVCA (P < 0.01); candoxatril + losartan(full dose) and OMA can decreased the effect of ISO (P < 0.01) .2)ISO increased AngⅡcontent〔（741±89）ng/L,（682±66）ng/L and（479±62）ng/L respectively〕significantly and the ANP and BK level mildly compared to control. Compared to myocardial hypertrophy control group, candoxatril + losartan (full dose)and OMA both decreased plasma AngⅡ content and increased the ANP〔（117±33）μg/L,（298±91）μg/L,（288±95）μg/L respectively〕and BK〔（124±12）ng/L,(232±21) ng/L and (309±24）ng/L respectively〕level significantly (P < 0.01), but candoxatril + losartan make less BK level increase than OMA (P < 0.05).3) OMA down-regulated the expression of p-PI3K, p-Akt protein which is not better than candoxatril + losartan(full dose). Conclusion candoxatril combined losartan and OMA decrease myocardial hypertrophy in rats. There were differences in the plasma hormone level.