Chronic Treatment of a Mouse Model of Cerebral Amyloid Angiopathy and Brain AT(1) Receptor Expression

慢性治疗小鼠脑淀粉样血管病模型及脑AT(1)受体表达

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Abstract

INTRODUCTION: The renin-angiotensin-aldosterone system (RAAS) has been shown to be dysregulated in dementia, with elevated levels of angiotensin-converting enzyme (ACE), angiotensin (Ang) II, and Ang II type 1 receptors (AT(1)Rs). Cerebral amyloid angiopathy (CAA), a common cerebrovascular disease, currently has no treatment or cure available. We aimed to determine if a mouse model with CAA (Tg-SwDI) also exhibits elevated levels of AT(1)Rs and whether RAAS-targeting drugs (telmisartan and lisinopril) mitigate these effects. MATERIALS AND METHODS: Tg-SwDI mice were treated with sub-depressor doses of either telmisartan or lisinopril from 3-8 months of age, with blood pressure being monitored 2 and 4 months after the start of treatment. Postmortem, receptor autoradiography was performed to determine levels of AT(1)R in 13 brain regions in untreated and treated Tg-SwDI mice compared to wild-type controls (C57Bl/6J). RESULTS: No statistically significant differences among groups were observed in any of the 13 regions analyzed. However, trends with medium to large effect sizes were observed. CONCLUSIONS: CAA did not significantly dysregulate AT(1)R levels in the brains of Tg-SwDI mice compared to wild-type mice. Drug treatment caused no significant brain AT(1)R alterations. Further studies are required to determine if the trends observed are pathophysiological and pharmacologically significant.

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