奥米沙坦改善压力负荷诱发心肌肥厚机制

Objectives: This study is designated to investigate whether Olmesartan regresses cardiac hypertrophy induced by pressure overload in the absence of angiotensin II in mice. Methods: Pressure overload was produced by constriction of the transverse aorta (TAC) Wild Type (WT) C57BL/6J and angiotensinogen-deficient (ATG KO) mice of 8-10 weeks were respectively divided into three groups: sham-operated group (n=5 and n=5), TAC plus Saline group (n=10, n=9) and TAC plus Olmesartan group (n=9 and n=9). After 2 weeks of TAC, echocardiography assessments were performed for the geometry and functions of hearts, and then mice were subjected to catheterization to measure the left ventricular end-systolic pressure (LVESP) and left ventricular end-diastolic pressure (LVEDP). Only the mice with more than 155mmHg and less than 180mmHg were considered to be successfully TAC-operated and were used for statistic analysis .Cardiac hypertrophy was confirmed further by histological analysis on the cross-sectional area (CSA) of cardiac myocytes in left ventricle and mid-transverse sectional area (MSA, heart weight to body weight of ratio (HW/BW) , and the expression of the genes related to cardiac hypertrophy such as atrial natriuretic peptide (ANP), skeletal a-actin (SAA) and ventricular natriuretic peptide (BNP). Results: The haemodynamics analysis showed no significant differences between WT and ATG KO mice after TAC. Olmesartan can markedly abolish the increase of LVAWTd, LVPWTd, LVPWTs, CSA and MSA and significantly inhibit the upreguration of special gene expressions induced by pressure overload not only in WT mice but also in ATG KO mice. Conclusions: Omlesartan can abrogate pressure overload-induced cardiac hypertrophy in of AngII.