Study On The Effect Of Estrogen On Renin-Angiotensin-Aldosterone System

Objective:To investigate the effect of estrogen onRenin-Angiotensin-Ald osterone System .Methods:1.Twelve-week-old female Sprague-Dawley rats were randomly allocated to three groups:1)sham operation(control);2)ovarietomy(ovx); 3)ovariectomy +estrogen(ovx+E2). One week after ovariectomy, the rats were assigned to ovariectomy or estrogen treatment groups. The control group did not undergo ovariectomy.2. Vascular smooth muscle cells from 8-week-old Sprague-Dawley rats were cultured. The effect on the expression of AT,-R mRNA was detected by RT-PCR.Result:1.Serum estradiol concentration were significantly lower in ovariectomized rats than in sham-operated animals. Estrogen replacement therapy led to a reconstitution of physiological estradiol level.2) The systolic blood pressure(SBP) was significantly higher in ovariectomized rats than that of sham-operated rats. No difference was observed between ovariectomized rats with estrogen replacement therapy(ERT)and sham-operated animals. 3)Plasma concentration of angiotensin II was significantly increased after ovariectomy .Estrogen treatment significantly decreased it. 4) No differences could be observed between the study groups with regard to the serum aldosterone levels . Serum cholesterol was increased and high-density lipoprotein was decreased after ovariectomy . Serum triglyceride was only slightly increased afterovariectomy. Ovariectomized rats treated with estrogen decreased the level of cholesterol,but significantly elevated both triglyceride and high-density lipoprotein . 3)AT1-R mRNA levels in tissue extracted from heart, kidney cortex and aorta were significantly increased in ovatiectomized rats compared with sham-operated animals .Estrogen replacement therapy in ovariectomized reversed AT1-R mRNA overexpression. Electron-microscopic study on kidney cortex found that ovariectomy led to glomerulosclerosis , however estrogen replacement therapy failed to attenuate glomerular injury.2. The direct influence of estradiol on AT1-R mRNA expression was investigated in VSMCs . Estradiol (1 u mol/L) led to time-dependent downregulation of AT1-R mRNA expression, with a maximum peak after 12 hours corresponding to an decreasing by 22%. Estradiol caused a concentration-dependent downregulation of AT,-R mRNA in VSMCs. Conclusion:1. The renin-angiotensin system was activated after ovarietomy inrats , as plasma concentration of angiotensin II and AT1-R mRNA levels in tissue extracted from heart, kidney cortex and aorta were significantly increased.These effects were reversed by ERT.2. Estrogen downregulated AT1-R mRNA expression in vitro and in vivo.3. SBP was increased in ovarietomized rats, ERT could prevent the increase of SBP.4. ERT could improve the lipid metabolism.5. Ovariectomy led to glomerulosclerosis in rats, however estrogenreplacement therapy failed to attenuate glomerular injury.