| Background Hypertension is a vital syndrome, and it takes participation in thedevelopment of many kinds of diseases. Therefore, to reduce and even eliminatehypertension have a very important clinical significance to the target organ harm.Already confirmed, the development of hypertension seriously influences thestructure and function of heart, and this kind of change also occures in themyocardial cells. Endoplasmic reticulum stress (ERS) is a kind of stressresponse in cell. It is a pathology process in cell organ, which is caused byendoplasmic reticulum homeostasis unbalanced and physiological function ondisorder because of some reasons. Many researches indicate: ERS play aimportant role in coronary disease, diabetes, and so on. But in the formingprocess of hypertension, the problems that if does ERS take effect on thisprocess, and what is its mechanism are still needed to research. Angiotension II (AngII) is one of the most important factors for cardiac myocyte apoptosis.AngII combining with AT1 recceptor can cause cardiac myocyte apoptosis. Theresearch indicated: The angiotensin converting enzyme inhibitors (ACEI) canalleviat cardiac myocyte apoptosis in hypertension. But the research about thatERS take participation in the process that ACEI alleviats cardiac myocyteapoptosis is not yet clearly at present.ObjectiObjective This study was therefore designed to observe in the expression ofglucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP)in rat heart after aortic constriction, which are mainly expressing in ERS, and therelations among them with cardiac myocyte apoptosis; to inveting the effect andmechanism of ACEI in alleviating cardiac myocyte apoptosis in hypertension.The purpose of the study is to seek for the inner relations between hypertensionand ERS, and for preventing and controlling hypertension finally to providenovel theoretical evidences and new target spots of treatment.Methods In this study, the rats which received abdominal transverse aorticconstriction (TAC) were used as experiment models. Carotid artery cannulationwas used to measure the blood pressures. Western blot andimmunohistochemistry was used to assess the protein level of GRP78 and CHOP.TUNNEL was used to detect the cardiac myocyte apoptosis. All methods wereappled to identify: (1) the changes of expressions of GRP78 and CHOP proteinon 3d, 7d, 14d and 28d after TAC in heart during hypertension forming; (2) thechanges of cardiac myocyte apoptosis on 3d, 7d, 14d and 28d after TAC inmyocardial cells during hypertension forming; (3) the effect of ACEI on theexpressions of GRP78 and CHOP protein; (4) the effect of ACEI on cardiacmyocyte apoptosis.Results (1) Compared with Sham group, the mean arterial pressures of rats in TAC group increased significantly on 3d after TAC, and increased progressivelyduring the experiment (P<0.05). (2) On 3d after TAC, the protein level of GRP78in TAC group was increasing compared with control group (P<0.05), but itsexpression was lower than on 7d,14d and 28d(P＜0.05). On 7d after TAC, theprotein level in TAC group was the highest. And on 14d,28d it decreased,butstill sustained high level during the experiment afterwards compared with Shamgroup(P<0.05). (3) After TAC, The protein level of CHOP in TAC groupsincreased progressively, and which were all higher than their Sham group(P<0.05), except on 3d (P>0.05). (4) On 7d after surgery in both TAC group andSham group the cardiac myocyte apoptosis could be detected by TUNNEL, andthe incidence of cardiac myocyte apoptosis increased progressively. Theincidence of cardiac myocyte apoptosis in TAC group on 28d after TAC was30.23±0.17%, which was the highest. (5) Correlation analysis indicated anegative correlation between mean arterial pressure and GRP78 proteinexpression in TAC group from 7d after TAC (r=-0.999,P=0.034), and a positivecorrelation between mean arterial pressure and CHOP protein expression(r=0.996,P=0.004. It also indicated a negative correlation between CHOPprotein expression and GRP78 protein expression (r=-0.979,P=0.042), and apositive correlation between CHOP protein expression and the incidence ofcardiac myocyte apoptosis (r=0.998,P=0.001). (6) The mean arterial pressure ofrats in Cartopril group was 124.67±6.26mmHg, significantly lower than the ratsin TAC group (169.73±6.58 mmHg), but higher than the rats in Sham group(117.08±7.92 mmHg), the devation was statistically significant (P<0.05). (7)The mean optical density of GRP78 in the rats in Cartopril group was 0.20±0.02,significantly lower than the rats in TAC group (0.35±0.03), but slightly higherthan the rats in Sham group (0.16±0.03), the devation was statistically significant (P<0.05). (8) The mean optical density of CHOP in the rats inCartopril group was 0.23±0.03, significantly lower than the rats in TAC group(0.46±0.05), but slightly higher than the rats in Sham group (0.07±0.02), thedevation was statistically significant (P<0.05). (8) Cartopril group showed asmall amount of apoptosis in cardiac myocytes (18.73±0.28%), significantlylower than the TAC group (31.67±0.54%), but slightly higher than the Shamgroup (13.49±0.12%), the devation was statistically significant (P<0.05); theincidence of cardiac myocyte apoptosis in TAC group was significantly higherthan the ones in Sham group, and the devation was statistically significant(P<0.05).Conclusions Hypertension caused by TAC induces the endoplasmic reticulumstress. At the early stage of hypertension, the expression of GRP78 gets thesuperiority status. While prolonged ERS activated by hypertension induces asignificant up-regulation in CHOP, CHOP could participate in myocyte apoptosisin hypertension, and also cause the regulation disequilibrium of endoplasmicreticulum stress. Captopril can has a protective effect of myocardial cellapoptosis, through reducing the level of ERS.
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