Amlodipine decreases myocardial endoplasmic reticulum stress in rats with abdominal aortic banding hypertension / 基础医学与临床

ABSTRACT

Objective To study the expression of protein 94 (GRP94) and C/EBP-homologous protein (CHOP) in myocardial tissue of hypertensive rats and to investigate the effects of amlodipine on endoplasm retieulum stress ( ERS) and ventricular hypertrophy in abdominal aortic banded rats .Methods One hundred and twenty adult male SD rats with criteria were divided randomly into three groupssham-operated group , abdominal aortic banding ( AAB) and AAB treated with amlodipine (AAB+Aml)groups(n=40).In sham-operated rats, the abdominal aorta was isola-ted but not constricted , while the abdominal aorta were constricted in AAB rats .The AAB+Aml group was treated by abdominal aortic constriction and treated with amlodipine [10 mg/(kg· d)].According to the time of surgery, each group was further divided into 2, 4 and 8-week postoperative subgroups ( n=6 ) .Mean arterial pressure (MAP), the 1eft ventricular mass (LVM) and body mass (BM) were measured and (LVM/BM) was calculated. The morphology of cardiomyocytes was observed by HE staining .The protein level of GRP 94 and CHOP was ana-lyzedbyimmunohistochemistryandwesternblot.Results 1)Withtimeaftersurgery,MAPandLVM/BWof AAB group increased gradually , and they were obviously higher than the sham operation group [ MAP 2 weeks (144 ±10)vs(118 ±9), 4 weeks (163±8)vs(120±7), 8 weeks(177±10)vs(120±6)mmHg;LVW/BW2 weeks (2.21±0.17) vs (1.91±0.12), 4 weeks (2.45±0.16) vs (2.01±0.14), 8 weeks (2.68±0.15) vs ( 2.05 ±0.09 ) mmHg;( P<0.05 ) ] .The cardiomyocytes in AAB group were hypertrophic as compared to the sham group.The expression of GRP94 in AAB group increased significantly at 2 weeks post-operation, and reached peak level at 4 weeks after the surgery and was on the decline thereafter .The expression of CHOP and GRP94 in AAB rats were significantly higher than sham group, and reached the peak at the 8 weeks after surger-y.2)Treatment with amlodipine significantly reduced MAP and LVM/BW in AAB rats[(MAP2 weeks (126± 6) vs (144±10), 4 weeks (125±8) vs (163±8), 8 weeks (128±5) vs (177±10)mmHg;LVM/BW2 weeks ( 1.94 ±0.15 ) vs ( 2.21 ±0.17 ) , 4 weeks ( 2.13 ±0.08 ) vs ( 2.45 ±0.16 ) , 8 weeks ( 2.18 ±0.10 ) vs ( 2.68 ± 0.15)mg/g;(P<0.05)].The myocardial hypertrophic was alleviated in AAB+Aml group.The level of GRP94 and CHOP in AAB+Aml group was lower than those in AAB rats ( all P<0.05 ) .Conclusions Endoplasmic reticulum stress is involved in the ventricular remodeling caused by hypertension , and use of amlodipine can reduce ventricu-lar hypertrophy in hypertension models possibly by inhibiting endoplasmic reticulum stress via down -regulation of GRP94 and CHOP .