Protective Effects Of Amlodipine Against Left Ventricular Hypertrophy Caused By Endoplasmic Reticulum Stress In Rats

Hypertension is a syndrome of cardiovascular disease. Long-term pressure load cancause cardiomyocyte hypertrophy and ventricular remodeling, resulting in compensatoryincreasing of cardiac function. Because of hypertrophy myocardial over-oxygen demandand insufficient blood flow of coronary arteries, the compensatory function will causemyocardial ischemia and decline of myocardial contractility, which will eventually causeserious damage to our bodies.Endoplasmic reticulum stress(ERS) is a kind of reaction at a cellular level.It is aself-protection way of cell when endoplasmic reticulum homeostasis has been destroyed.At early stage, ERS can keep ER Homeostasis by triggering unfolded protein response.However, if stress is severe and/or prolonged, the ER also initiate apoptotic signaling,which lead to cell death. Recent studies have showed that ERS is implicated in thepathophysiology of various cardiovascular diseases, such as coronary disease,heart failure,diabetic cardiomyopathy, dilated cardiomyopathy. But it is still unclear whether ERS hashappened in hypertension and how it affect myocardium. Amlodipine is a new type of calcium channel blockers. It is a common clinical drugbecause of its stable pressure lowering, less side-effects and target organs-protectionfunctions. However, the specific molecular mechanism of target-protection effect remainsunclear. According to this situation, we established hypertension rat model and giveamlodipine intervention, by observing the changes of ERS signal expression in myocardialtissue, to investigate the molecular mechanism of ERS in myocardial tissue and themolecular mechanism of amlodipine reversing left ventricular hypertrophy, to support theclinical application of amlodipine.Aim:We established abdominal aortic banding hypertensive rat model, to investigate theinfluence of amlodipine on the expression of GRP94and CHOP in rat myocardial tissueand the effects of it against left ventricular hypertrophy.Methods:Hypertension rats were used as experiment models by abdominal aortic stenosissurgery in this study.①Mean blood pressure(MBP)was measured through carotidmanometry.②The1eft ventricular mass(LVM) and body mass(BM) were measured andLVMI(LVM/BM) was calculated.③M yocardial cell morphology were observed by HEstaining.④Immunohistochemistry and Western blot were used to evaluate the proteinlevels of GRP94and CHOP.Results：The MBP，LVWI, as well as expression of GRP94and CHOP in myocardial tissuewere remarkably increased in AAB group when compared with sham group(P<0.05)，while amlodipine could significantly decrease MBP, LVWI and down-regulate theexpressions of GRP94and CHOP in myocardial tissue (P<0.05).Conclusion： The endoplasmic reticulum stress may be involved in the left ventricularhypertrophy caused by hypertension．Amlodipine may exerts an protective effect on heartby inhibiting the endoplasmic reticulum stress via down-regulating the expression ofGRP94and CHOP.