Angiotensin II receptors and neuroprotection

It is well recognized that stroke and related cerebral ischemia is one of the most common causes of mortality in the developed world, not to mention the immense burden of morbidity and disability that afflicts stroke survivors. It is also well recognized that blood pressure (BP) control is critical in reducing the incidence of stroke (MacMahon et al. 1990). On this point, drugs that inhibit the rennin-angiotensin system (RAS) are increasingly used in preventative strategies against stroke or recurrent stroke (HOPE 2000; PROGRESS 2001; Dahlof et al. 2002). However, as will be discussed, data from animal studies investigating stroke also suggest that part of the neuroprotective effect of AT1 receptor antagonists is independent of BP. This fact also points to direct central interference of the brain RAS, which was originally described over 3 decades ago (Unger et al. 1988; Steckelings, Bottari, and Unger 1992).