Effect Of Calcium Channel Blocker Combined With Varying Degrees Of Inhibition Of Angiotensin ? Type 1 Receptor On Left Ventricular Hypertrophy In Ovariectomized Spontaneous Hypertensive Rats

Objective : The aim of this study was to investigate the effect of varying degrees of inhibition angiotensin ? type 1 receptor?AT₁R?on left ventricular hypertrophy?LVH?in ovariectomized?OVX?spontaneous hypertensive rats?SHR?by administering calcium channel blocker?CCB?combined with different dose valsartan.Methods: The 12-week-old female SHR?n=45?were submitted to OVX or a surgical procedure without ovary removal?Sham?and formed three groups: group A: Sham + amlodipine?5mg/kg/d?+Valsartan 30mg/kg/d?n=15?,group B: OVX+ amlodipine?5mg/kg/d?+Valsartan 15mg/kg/d?n=15?and group C: OVX+ amlodipine?5mg/kg/d?+Valsartan 30mg/kg/d?n=15?.After four weeks of operation,serum estrogen levels were measured by radioimmunoassay and vaginal smear in order to determine successful postmenopausa models.After the postmenopausa model was established successfully,interventricular septal thickness?IVST?and left ventricular posterior wall thickness?LVPW?of model rats were evaluated by echocardiography to determine LVH.Before and after 12 weeks of intervention,the following experimental measurements were performed:?1?Systolic blood pressure?SBP?,diastolic blood pressure?DBP?and mean blood pressure?MBP?of SHR were measured by tail artery pressure?n=6?;?2?Echocardiography of SHR: interventricular septal thickness?IVST?,left ventricular posterior wall thickness?LVPW?.?3?Hemodynamic parameter: heart rate,left ventricular systolic pressure?LVSP?,left ventricular end-diastolic pressure?LVEDP?,±dp/dt.?4?angiotensin ??Ang??,angiotensin?1-7?[Ang?1-7?],angiotensin?1-9?[Ang?1-9?],angiotensin-converting enzyme 2?ACE2?and angiotensin-converting enzyme?ACE?were detected by enzyme-linked immunosorbent assay?ELISA?analysis.?5?The expression of angiotensin II type 1 receptor?AT1R?,angiotensin II type 2 receptor?AT2R?and Mas R in myocardium was measured by Western-blot.?6?The hematoxylin-eosin staining was used to observe pathological morphology changes of the left ventricular tissues.All the above data were statistically analyzed by SPSS23.0 software.The data were expressed by mean ±standard deviation.One way ANOVA was adopted to compare the difference of these groups.The difference was statistically significant?P < 0.05?.Results:?1?After four weeks of operation,level of estrogen in OVX group was significantly lower compared with Sham group?33.85±3.71 vs 55.60±2.06 pg/ml,P < 0.05?.Vaginal smears of OVX-SHR: non-estrus,small round cells,less cytoplasm.These results judged as the successful of menopause model establishing?2?Blood pressure in SHR: compared with Sham-SHR,SBP,DBP and MBP in OVX-SHR were significantly increased?all P < 0.05?.After the treatment,the blood pressure of each group significantly reduced.But there were no difference in ?SBP,?DBP and ?MBP among group A,group B and group C?P > 0.05?.?3?Cardiac echocardiographic parameters: ovariectomy had negative effect on IVST and LVPW compared with Sham-SHR,while there were no difference in ?IVST and ?LVPW among group A,group B and group C.?4?Compared with Sham-SHR,LVESP and +dp/dt decreased in OVX-SHR,while LVEDP increased.?5?The level of Ang? and ACE2 in group A was lower when compared with group B?P < 0.05?.The level of Ang?1-7?and Ang?1-9?in group C was higher when compared with group A and group B?P < 0.05??6?The expression of AT1 R in group A was lower when compared with group B and group C.compared with group B and group C the expression of AT2 R and Mas R in group A was higher?P < 0.05?.Compared with group B,the expression of AT1 R in group C was lower and the expression of AT2 R and Masr was higher?P < 0.05?.Conclusion: On the basis of optimal blood pressure control,CCB combined with varying degrees of inhibition of AT1 R has different effect on the left ventricular structure and function caused by hypertension after estrogen deficiency.The LVH of OVX-SHR was significantly improved by greater degree of block of AT₁ R.