Do RAS Inhibitors Protect the Brain from Cerebral Ischemic Injury?
Naohisa Hosomi, Akira Nishiyama and Masayasu Matsumoto
Affiliation: Department of Clinical Neuroscience & Therapeutics, Hiroshima University Graduate School of Biomedical & Health Sciences, 1-2-3, Kasumi, Minami-ku, Hiroshima, Hiroshima 734-8551, Japan.
Keywords: Brain, cerebral ischemia, renin-angiotensin system, angiotensin type 1 receptor, angiotensin receptor blocker.
In addition to centrally regulating electrolyte homeostasis and blood pressure, angiotensin IIhas various general
effects on the central nervous system. The existence of renin-angiotensin system components in the brain has been well
established. Angiotensin II and other renin-angiotensin system components are synthesized and distributed throughout the
brain. Post-ischemic oral administration of a non-hypotensive dose (1/10th of the clinical dose) of angiotensin receptor
blocker (ARB) has protective effects on reducing cerebral ischemic injury and improving neurological outcomes. Brain
tissue angiotensin II levels transiently increase after reperfusion through the local generation of angiotensin IIand not via
the transudation of plasma angiotensin II. Systemic administration of ARBs decreases brain tissue angiotensin II in both
the intact and ischemic brain tissue via downregulation of angiotensinogen and angiotensin-converting enzyme mRNA
expression, although plasma ARB barely crosses the blood-brain barrier during systemic ARB treatment. Only
hypotensive dose of ARB treatment opens leptomeningeal anastomoses. Therefore, systemic ARB treatment shows
neuroprotective effects not through increasing collateral perfusion but decreasing brain tissue angiotensin II in a nonhypotensive
Rights & PermissionsPrintExport