Effects of Candesartan on Angiotensin II Receptors in Left Ventricular Hypertrophy in Rats

Background and Objective Angiotensin Ⅱ receptor blocker (ARB) has been reported to have protective effects on the cardiovascular disease. However,the mechanism governing the effects of ARB is incompletely understood. The present study was designed to detect the expression of Ang Ⅱ receptors in left ventricular hypertrophy(LVH) and determine whether ARB improve the left ventricular remodeling by blockade of AT1R itself or by concomitant stimulation of AT2R. Methods Twenty-one male Sprague-Dawley rats were divided into three groups: sham group(distilled water,n=7);myocardial hypertrophy group(n=7);candesartan group [10 mg/(kg·d),n=7] by gavage for 6 week. Left ventricular hypertrophy model was established by abdominal aortic stenosis. Rats were sacrificed and the blood and hearts were collected. The expression of AT1R and AT2R was detected by immunohistochemistry (IHC) and RT-PCR,respectively. Left ventricular mass index(LVMI),cross-sectional area(CSA),apoptosis index(APOI),and the level of plasma Ang Ⅱ were determined. Results BP,LVMI,CSA,APOI,level of plasma Ang Ⅱ and expression of AT1R and AT2R in myocardial hypertrophy rats were markedly increased as compared with sham group (all P0.01). Candesartan significantly decreased BP,LVMI,CSA (all P0.01,CSA P0.05),and markedly increased APOI(P0.05,P0.01,respectively). Concomitanly,candesartan decreased the expression of AT1R protein and mRNA(P0.05,P0.01,respectively) with little changes in AT2R protein and mRNA(P0.05). However,the level of AT1R and AT2R protein and mRNA in candesartan group were all increased obviously (P0.05,P0.01 respectively) as compared with sham group. AT2R/AT1R were markedly increased as compared with myocardial hypertrophy group and sham group (P0.01). Conclusions Expression of AT1R and AT2R receptors increased obviously in cardiomyocyte in rat with LVH,indicating that AT1R and AT2R both participate in the process of LVH. Candesartan prevented left ventricular hypertrophy effectively which may be mediating blockade of AT1R,and activation of AT2R.