Effect Of Heart Remodeling And Cardiac Myocyte Apoptosis In Juvenile Spontaneously Hypertensive Rats Under The Intervention Of Antihypertensive Drugs

OBJECTIVS. This study was performed to observe the effect of heart remodeling and cardiac myocyte apoptosis and the correlation between them in juvenile spontaneously hypertensive rats under the intervention of antihypertensive drugs,to investigate the mechanisms of preventive therapy to improve heart remodeling and the role and meaning of cardiac myocyte apoptosis in earlier period of hypertension.METHODS. 36 spontaneously hypertensive rats (SHR) aging 4 weeks (24 male and 12 female) were divided into 6 groups according to random blocks design. Treated rats were given one of the following drugs for 6 weeks before they were killed:the adrenoceptor blocker propranolol (50mg/kg.d),the angiotensin-converting enzyme inhibitor enalapril (30mg/kg.d),the calcium channel blocker nifedipine(35mg/kg.d),the ATr receptor antagonist valsartan (30mg/kg.d),or the diuretic hydrochlorothiazide (75mg/kg.d). Another group was set up as controlling. The cardiac ponderal index (CPI),the left ventricular hypertrophy index (LVHI) and the right ventricular hypertrophy index (RVHI) were calculated by dividing the weight of the ventricles (HW),the left ventricular (LVW,including the interventricular septum) and the right ventricular (RVW) by the body weight (BW) and multiplying that value by 100. Cardiomyocyte apoptosis was assessed in the free wall of left ventricular by in situ TdT-mediated dUTP nick end labeling (TUNEL). Semi-quantitative analysis was used to calculate cardiac myocyte apototic index (CMAI,calculated by dividing the number of apoptotic myocyte nuclei by the total number of myocyte nuclei and multiplying that value by 100). The morphologic change of apoptotic cardiac myocyte was observed under transmission electron microscope.RESULTS. 1. The CPI and LVHI apparently lowered inenalapril or valsartan group compared with controlling group (p<0.05,p<0.01). The CMAI rose notably in enalapril or nifedipion or valsartan group compared with controlling group (p<0.01,p<0.001). The CPI and LVHI trended to descend in propranolol and nifedipion groups,the CPI and LVHI trended to go up in hydrochlorothiazide group,and the CMAI trended to go up in propranolol group compared with controlling group but all showing no statistic meanings (p>0.05). 2. The CPI and LVHI descended significantly and the CMAI rose notably in SHR under enalapril or valsartan intervention compared with hydrochlorothiazide group (p<0.01). The LVHI obviously lowered in valsartan group compared with propranolol and nifedipine groups (p<0.05). The CMAI obviously heightened in enalapril or valsartan groups compared with propranolol group (p<0.05). There were no apparently differences among the means of the RVHI (p>0.05). 3. There was a positive correlation between the LVHI,RVHI and the CPI in juvenile SHR (the former tr=11.901,r=0.898,p<0.001;the latter tr=3.911,r=0.557,p<0.001). A negative correlation was found between the CPI or the LVHI and CMAI (the former tr=4.668,r= - 0.625,p<0.001;the latter tr=5.320,r= - 0.674,p<0.001). 4. Electron microscope features of cardiac myocyte apoptosis (including intact sarcolemma in the presence of cytoplasm compaction and segregation of nuclear chromatin into small sharply delineated electron dense masses that abut the nuclear envelope) were discovered easily in enalapril,nifedipine and valsartan groups. The ultramicrostructural changes,such as cardiac cellular hypertrophy,sarcoplasmic reticulum expansion,mitochondrion hyperplasia,were examined easily in hydrochlorothiazide and controlling groups.CONCLUSIONS . 1. Our data suggests that dysregulation between the cardiac myocyte proliferation and apoptosis occurs even in juvenile SHR,resulting in the increase of heart weight and the heart remodeling. 2. There are different effects on heart remodelingand cardiac myocyte apoptosis in juvenile SHR under the intervention of different antihypertensive drugs,indicating distinct mechanisms among these drugs in improving the heart remodeling.3. The improvement of genetic heart remodeling in hypertension under a...