title: Do RAS inhibitors protect the brain from cerebral ischemic injury?
abstract: 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 dose.
authors: Department of Clinical Neuroscience & Therapeutics, Hiroshima University Graduate School of Biomedical & Health Sciences, 1-2-3, Kasumi, Minami-ku, Hiroshima, Hiroshima 734-8551, Japan. nhosomi@hiroshima-u.ac.jp
authors: Naohisa
authors: N
authors: Hosomi
authors: Akira
authors: A
authors: Nishiyama
authors: Masayasu
authors: M
authors: Matsumoto
mesh_terms: D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use*; D001812:Blood-Brain Barrier; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D012084:Renin-Angiotensin System / Q000187:drug effects*
chemical_list: D057911:Angiotensin Receptor Antagonists