Role Of Angiotensin-(1-7) On Cognitive Function In Rats With Chronic Cerebral Hypoperfusion

Objective:To investigate the role of Ang-(1-7) on cognitive function in rats with chronic cerebral hypoperfusion.Methods:Permanent, bilateral common carotid artery occlusion(2VO) and sham-operation models were performed in ninty animals weighing300-350g. And two months later, the rats were subjected to two-week intracerebroventricular infusion of sterile saline (0.5μl/h), low-does Ang-(1-7)(100pmol/0.5ul/h), high-does Ang-(1-7)(10nmol/0.5μl/h), high-dose Ang-(1-7)＋A-779(10nmol/0.5ul/h), A-779(10nmol/0.5ul/h) using Alzet osmotic minipumps. Accordingly, they were divided into the control group (sham operation＋sterile saline), the sterile saline group (2vo+sterile saloine), the Ang-(1-7) group[2vo＋Ang-(1-7)] and the Ang-(1-7)+A-779group[2vo＋Ang-(1-7)＋A-779]. Before and during the treatment, systolic blood pressure (SBP) was measured by the tail cuff method. After two weeks of continuous intracerebroventricular infusion, cognitive performance was assessed by Morris water maze, the levels of Mas, eNOS, iNOS and nNOS were analyzed by western blotting, and the neuronal survival were assessed using immunohistochemistry.Results:After2-VO induction, mean systolic blood pressure was remarkably increased by30-40mmHg over the baseline, though no significance changes were showed after Ang-(1-7) infusion and Ang-(1-7)+A-779infusion. Moreover, CCH-induced cognitive deficit was significantly attenuated by Ang-(1-7) infusion. As compared with the control rats, the Mas and eNOS expression was significantly inhibited by the induction of2-VO, which was then reversed by Ang-(1-7) infusion. However, the levels of iNOS and nNOS were not affected neither by2-VO induction nor Ang-(1-7) infusio, Then,2-VO-promoted apoptosis in the hippocampal CA1area was suppressed by Ang-(1-7), and the benefits were prevented by A779, confirming the involvement of Mas.Conclusion:Ang-(1-7) can prevented neuronal apoptosis, partly through upregulate the expression of Mas and enos, which might be the underlying mechanism of ameliorating the cognitive dysfunction in CCH rats.