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  • Title: Lacidipine inhibits endoplasmic reticulum stress and myocardial remodeling induced by pressure overload in rat heart.
    Author: Huai Y, Wang H, Zhao L, Zhao L, Pei J.
    Journal: Eur J Pharmacol; 2013 Oct 15; 718(1-3):441-7. PubMed ID: 23911888.
    Abstract:
    We undertook this study to investigate the influence of lacidipine on endoplasmic reticulum stress (ERS) and myocardial remodeling under pressure overload conditions. Thirty male Sprague Dawley rats were randomly divided into three groups: sham, transverse aortic constriction (TAC), and TAC+lacidipine groups. Invasive hemodynamics was measured. The structure of the left ventricle was observed via echocardiography. ERS parameters such as calreticulin (CRT) and caspase-12 expressions in cardiomyocytes were examined by immunohistochemistry. TUNEL staining was used to detect cardiomyocyte apoptosis. Left ventricular end-diastolic pressure (LVEDP), interventricular septal thickness (IVST), left ventricular posterior wall thickness (LVPWT), left ventricular weight index (LVWI), CRT and caspase-12 expression in cardiomyocytes were evaluated. The incidence of cardiomyocyte apoptosis significantly increased in the TAC group compared with the sham group (P<0.01). Meanwhile, left ventricular end-systolic pressure (LVESP), ejection fraction (EF), and early diastolic blood maximum flow rate of mitral valve/late diastolic blood flow velocity of mitral valve (E/A) values decreased significantly (P<0.01). LVEDP, IVST, LVPWT, and LVWI values and the incidence of cardiac apoptosis in the TAC+lacidipine group decreased significantly compared with those in the TAC group. CRT and caspase-12 expressions in cardiomyocytes were also significantly downregulated (P<0.05). On the other hand, LVESP, EF, and E/A values in the TAC+lacidipine group substantially increased (P<0.05). Our results suggest that lacidipine attenuates hypertrophied myocardial remodeling accompanied by inhibiting CRT and caspase-12 expression and cardiomyocyte apoptosis in rats subjected to TAC.
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