| Objection①In the present study, we observe the dynamic changes of nitric oxide and tumor necrosis factor-αLevels of Plasma in renovascular hypertensive rats (RHR) during the development of hypertension and pathological change of cerebral vessels of these rats, then we study the possible pathogenesis of hypertension and the related cerebrovascular disease from the aspects of blood vessel endothelium dysfunction and Inflammatory reaction;②to compare differences with NO and TNF-αdynamic changes in two sub-groups of hypertension group ,we study the possibility of nitric oxide and tumor necrosis factor-αas the prediction index of cerebral vessels event. The aim of this study is to develop screening effective and simple Forecasting index for the hypertension patient prone to the relevant blood vessel of brain disease to provide the theory basis.Methods①Two-kidney,two-clip methods were used to copy the model of renovascular hypertension in rats;②Systolic blood pressure of preheated (37°C, 15 minutes) conscious rats was measured by an indirect tail-cuff sphygmomanometer before renal artery constriction and at weekly intervals after renal artery constriction;③The levels of serum NO and TNF-αin serum were measured by nitrate reductase and enzyme-linked immunosorbant assay( ELISA),respectively, at pre-operation, and w2 , w4 , w8 ,w12 , w16 after operation;④After 16 weeks, rat brains were terminally sectioned into 2mm-thick coronal sections.brain sections were stained with hematoxylin-eosin (HE) for routine light microsopic observation. Based on the pathological results of cerebral vessels, the hypertension group was divided into simple hypertension group(SHG) and hypertensive cerebral vessels lesion group (HCVLG).Results㈠the dynamic changes of blood pressure,nitric oxide and tumor necrosis factor-αin renovascular hypertensive rats①The incidence rate of hypertension in the RHR was 100% after 4 week, BP kept on time—dependent increasing after operation(P<0.001); After 2,4,8,12,16 week of postoperation, BP of hypertension group were markly higher than that of corresponding period in the sham-operated group(P<0.001).②The content of NO in RHR reached the peak at 2 week after operation ,which was significantly higher than that of preoperation (P <0.001); from 4 week of postoperation to 16W , the contents of NO in the RHR were assume time—dependent dropping (P<0.001 or P<0.05)and decreased markedly as compared with the corresponding time point in the Sham-operated group(P<0.0 or P <0.001).③the contents of TNF-αkeep on increasing after operation in the RHR,which were markly higher than that of corresponding period in the Sham-operated group(P<0.001);the contents of TNF-αin the RHR kept on time—dependent increasing from w2 to w8 after operation(P <0.001 or P<0.05).④the contents of NO after w4(including w4) negatively correlated with BP in the hypertensive group(r=-0.865,P <0.01 ),in addition, the contents of TNF-αpostively correlated with BP after operation(r=0.841, P<0.01 ).㈡the precaution influence of NO and TNF-αlevels of plasma on cerebrovascular disease in the RHR①Based on the cerebrovascular pathology, cerebrovascular lesions were observed in 31 of 43 hypertensive group(72%) in the HCVLG, two rats show intracerebral hemorrhage, one rat show cerebral infarction, which occupy 7% of the hypertension group,cerebrovascular pathology of HCVLG show that thickening of vessel wall and stenosis of lumen; however, there were no evident changes of cerebrovascular pathology in the Sham-operated group and SHG.②The postoperative BP of SHG were gradually advance,but range increase became dropping from w4 after operation, especially after w12, there was no statistically significant difference in w16 to w12 after operation. BP keep on increasing after operation in the HCVLG,BP of the latter stage were strikingly higher than that of the former stage in the HCVLG(P <0.001).from the fourth week, BP of HCVLG is significantly higher than that of SHG in the same period(P <0.001).③the contents of NO in SHG decreased from 4 week of postoperation, but the drop scope is slowing(P<0.05),there was no statistically significant difference in w12 after operation(P>0.05). the contents of NO in HCVLG were keeping on decreasing w4 after operation(P<0.001 or P<0.05),the contents of NO after 12,16 weeks in HCVLG were decreased markedly as compared with the corresponding time point in the SHG(P <0.001)④the contents of TNF-αkeep on increasing in w2 of postoperation(P <0.05), but no statistically significant difference from w4 of postoperation(P>0.05).the contents of TNF-αof HCVLG were increased markedly from w2 after operation( P < 0.001 or P<0.05).the contents of TNF-αin the HCVLG were strikingly higher than that of in the SHG from w4 to w16 in the same period(P <0.05 or P < 0.01).Conclusions①With the increasing of BP, NO contents of hypertensive rats increased early then decrease lately, TNF-αcontents kept on increasing in hypertensive rats.change in the HCVLG is more severely than that in the SHG, These fingdings suggest that vessel wall endothelial dysfunction and inflammation may involved in the process of hypertension, and them may connected with atherosclerosis and stroke.②Down-regulative activity of NO and up-regulative activity of TNF-αmay play a role in the the development of hypertension and correlated cerebrovascular pathogenesis in the RHR, it may play a precaution role in the process of atherosclerosis and stroke.
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