Chronic Treatment of a Mouse Model of Cerebral Amyloid Angiopathy and Brain AT1 Receptor Expression.

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 (AT1Rs). 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 AT1Rs 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 AT1R 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 AT1R levels in the brains of Tg-SwDI mice compared to wild-type mice. Drug treatment caused no significant brain AT1R alterations. Further studies are required to determine if the trends observed are pathophysiological and pharmacologically significant.