Effects Of Estrogen On Vascular Function And Renin Angiotensin System Components In Renovascular Hypertension Rats

Objective:To study the effect of estrogen level on vascular function in renovascular hypertension?RVH?rats and normal blood pressure rats,And the effect on the mRNA and protein expression of renin angiotensin system molecules in RVH rats.Methods:60 SD rats wear made two-kidney one-clip?2K1C?model of renovascular hypertension by clipping left renal artery,in wich 45 SD rats meanwhile were ovariectomized for establishing animal model of renovascular hypertension with low estrogen level?2K1C-OVX?,15 female SD rats wear established low estrogen not hypertension model by only removing both ovaries?OVX?,according to the type of operation the rats were divided into7 groups,respectively Sham-M group,Sham-F group,OVX group,2K1C-M group,2K1C-F group,2K1C-OVX group and 2K1C-OVX-E2 group;2K1C-OVX-E2group wear treated with subcutaneous 17?-estradiol 15?g·kg^-1/day.After 24 weeks,the blood pressure was measured by power lab,blood was taken and prepared serum and plasma,detected concentrations of estradiol,NO,Ang?,ET-1.Monitored concentration of Ang 1-7,MDA,NO and the activity of SOD in aorta tissue.Vasodilator responses to acetylcholine in the aortic rings of thoracic aorta were determined by isolated organ-bath technique.mRNA and protein expression levels of RAS related molecular in aorta tissue wear detected by RT-PCR and western blot method.Results:1)the effect of estrogen level on vascular function in RVH rats and normal blood pressure rats:There was no significant difference in SBP and DBP between groups.The plasma ET-1 level in the2k1C-F group was higher than that of the 2k1C-M group and the 2K1C-OVX group?P<0.05?,while the plasma ET-1 level in the 2K1C-OVX group was lower than that of the2K1C-M group and the 2K1C-OVX-E2 group?P<0.05?.The vascular NO content in2k1C-F group was higher than that in 2K1C-M group,2K1C-OVX group and2K1C-OVX-E2 group?P<0.05?;The vascular NO content in OVX group was lower than Sham-F?P<0.05?.SOD level in 2k1C-F group was lower than that of 2k1C-M group,2K1C-OVXgroup and 2K1C-OVX-E2 group?P<0.05?,while 2K1C-OVX group was higher than that in 2K1C-M group?P<0.05?.MDA level in 2K1C-OVX-E2 group was higher than that of 2k1C-F group and 2K1C-OVX group?P<0.05?;MDA level in OVX group was higher than Sham-F group and Sham-M group?P<0.01?.The endothelium-dependent relaxation rate of the thoracic aortic ring in the 2k1C-F group was lower than that in the 2k1C-M group,the 2K1C-OVX group and the 2K1C-OVX-E2group?P<0.05?,and the OVX group was lower than that in the sham-F group?P<0.05?.2)Effects of estrogen on RAS components:The content of Ang?1-7?in Sham-F group was higher than that in Sham-M group?P<0.05?.The plasma Ang?in 2K1C-OVX-E2group was higher than that of 2k1C-F group,2K1C-OVX group?P<0.01?.Plasma Ang?in Sham-F group was lower than that of Sham-M group and OVX group?P<0.05?.Compared with 2k1C-F group,the mRNA expressions of ACE1,AT1aR,AT1bR,eNOS,and protein expressions of AT1R in 2k1C-OVX group were significantly decreased?P<0.05?,while the mRNA expressions of ACE2 and protein expressions AT2R were significantly increased?P<0.05?.The mRNA expression level of AT1bR in2K1C-OVX-E2 group was significantly decreased?P<0.05?.Compared with the2k1C-OVX group,the mRNA expressions of eNOS and protein expression of AT1R in2K1C-OVX-E2 were significantly increased?P<0.05?.Conclusion 1)estrogen may damage vascular function of renovascular hypertension rats by activating oxidative stress and RAS system;2)high level of estrogen may activate AngII-ACE1-AT1R axis,while reducing ACE2 and AT2R expression.