title: Blockade of AT1 receptors protects the blood-brain barrier and improves cognition in Dahl salt-sensitive hypertensive rats.
abstract: BACKGROUND
  The present study tested the hypothesis that inappropriate activation of the brain renin-angiotensin system (RAS) contributes to the pathogenesis of blood-brain barrier (BBB) disruption and cognitive impairment during development of salt-dependent hypertension. Effects of an angiotensin II (AngII) type-1 receptor blocker (ARB), at a dose that did not reduce blood pressure, were also examined.
  
  
  METHODS
  Dahl salt-sensitive (DSS) rats at 6 weeks of age were assigned to three groups: low-salt diet (DSS/L; 0.3% NaCl), high-salt diet (DSS/H; 8% NaCl), and high-salt diet treated with ARB, olmesartan at 1 mg/kg.
  
  
  RESULTS
  DSS/H rats exhibited hypertension, leakage from brain microvessels in the hippocampus, and impaired cognitive functions, which were associated with increased brain AngII levels, as well as decreased mRNA levels of tight junctions (TJs) and collagen-IV in the hippocampus. In DSS/H rats, olmesartan treatment, at a dose that did not alter blood pressure, restored the cognitive decline, and ameliorated leakage from brain microvessels. Olmesartan also decreased brain AngII levels and restored mRNA expression of TJs and collagen-IV in DSS/H rats.
  
  
  CONCLUSIONS
  These results suggest that during development of salt-dependent hypertension, activation of the brain RAS contributes to BBB disruption and cognitive impairment. Treatment with an ARB could elicit neuroprotective effects in cognitive disorders by preventing BBB permeability, which is independent of blood pressure changes.
authors.affiliation: Department of Cardiorenal and Cerebrovascular Medicine, Kagawa University Medical School, Japan. nico@med.kagawa-u.ac.jp
authors.forename: Nicolas
authors.initials: N
authors.lastname: Pelisch
authors.forename: Naohisa
authors.initials: N
authors.lastname: Hosomi
authors.forename: Masaki
authors.initials: M
authors.lastname: Ueno
authors.forename: Daisuke
authors.initials: D
authors.lastname: Nakano
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Hitomi
authors.forename: Masaki
authors.initials: M
authors.lastname: Mogi
authors.forename: Kenji
authors.initials: K
authors.lastname: Shimada
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kobori
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Horiuchi
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Sakamoto
authors.forename: Masayasu
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Masakazu
authors.initials: M
authors.lastname: Kohno
authors.forename: Akira
authors.initials: A
authors.lastname: Nishiyama
mesh_terms: D000804:Angiotensin II / Q000032:analysis; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects; D003071:Cognition / Q000187:drug effects*; D003337:Corpus Callosum / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use; D007150:Immunohistochemistry; D008297:Male; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D020303:Rats, Inbred Dahl; D013599:Systole / Q000187:drug effects; D013777:Tetrazoles / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D007093:Imidazoles; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D012333:RNA, Messenger; D013777:Tetrazoles; D000804:Angiotensin II; C437965:olmesartan