title: Angiotensin II AT1 receptor blockade reverses pathological hypertrophy and inflammation in brain microvessels of spontaneously hypertensive rats.
abstract: OBJECTIVE
  The spontaneously hypertensive rat (SHR) is vulnerable to brain ischemia and stress and exhibits a chronically stimulated brain angiotensin II system, cerebrovascular hypertrophy, and inflammation. Pretreatment with angiotensin II type 1 (AT1) receptor antagonists protects from brain ischemia and from stress and prevents the development of stress-induced gastric ulcers in part by reducing inflammation in the gastric mucosa. We studied whether AT1 receptor antagonists could exert antiinflammatory effects in the brain vasculature as a mechanism for their protective effects against ischemia.
  
  
  METHODS
  Ten-week-old SHR and normotensive Wistar-Kyoto male rats received the AT1 receptor antagonist candesartan (0.3 mg/kg per day) or vehicle for 28 days via osmotic minipumps. We studied AT1 receptors, intercellular adhesion molecule-1 (ICAM-1), endothelial nitric oxide synthase (eNOS), and number of macrophages by immunohistochemistry and Western blots.
  
  
  RESULTS
  We found increased endothelial AT1 receptor expression of brain microvessels and middle cerebral artery of SHR. Brain AT1 receptor inhibition reversed the pathological vascular hypertrophy, increased and normalized eNOS expression, and decreased ICAM-1 expression and the number of adherent and infiltrating macrophages in cerebral vessels of SHR.
  
  
  CONCLUSIONS
  The antiinflammatory effects of AT1 receptor antagonists may be an important mechanism in protecting against ischemia.
authors.affiliation: Section on Pharmacology, Division of Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA.
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Ando
authors.forename: Jin
authors.initials: J
authors.lastname: Zhou
authors.forename: Miroslava
authors.initials: M
authors.lastname: Macova
authors.forename: Hans
authors.initials: H
authors.lastname: Imboden
authors.forename: Juan M
authors.initials: JM
authors.lastname: Saavedra
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology*; D001713:Biphenyl Compounds; D001921:Brain / Q000098:blood supply* / Q000473:pathology; D002545:Brain Ischemia / Q000517:prevention & control*; D002339:Carotid Arteries / Q000187:drug effects / Q000378:metabolism; D006984:Hypertrophy; D007249:Inflammation; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008262:Macrophage Activation; D008297:Male; D008833:Microcirculation / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013777:Tetrazoles / Q000494:pharmacology*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000893:Anti-Inflammatory Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D018696:Neuroprotective Agents; D013777:Tetrazoles; D018799:Intercellular Adhesion Molecule-1; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; C081643:candesartan