title: Protective effect of telmisartan on neurovascular unit and inflammasome in stroke-resistant spontaneously hypertensive rats.
abstract: OBJECTIVE
  Hypertension is a crucial risk factor for both stroke and dementia, including Alzheimer's disease (AD). We inspected the effect of telmisartan on the neurovascular unit (NVU) and related inflammatory responses in spontaneously hypertensive rat stroke resistant (SHR-SR) by observing the components of NVU such as N-acetyl glucosamine oligomer (NAGO), collagen IV, astrocytes, and matrix metalloproteinase-9 (MMP-9), as well as inflammasome NOD-like receptors family protein 3 (NLRP3).
  
  
  METHODS
  In the present study, we examined the effect of a highly selective angiotensin type 1 (AT-1) antagonist of angiotensin 2 receptor with high lipid solubility, telmisartan, on NVU and related inflammatory responses in SHR-SR with a low dose (0.3 mg/kg/day) only for improving metabolic syndrome, and a high dose (3 mg/kg/day) for improving both metabolic syndrome and SHR-SR hypertension.
  
  
  RESULTS
  Compared to normotensive Wistar rats, long-lasting hypertension in SHR-SR disrupted NVU by changing immunohistological components such as NAGO, collagen IV, astrocytes, and MMP-9. SHR-SR also strongly induced AD-related inflammasome NLRP3 in neuronal cells with age. However, such NVU disruption and inflammasome activation were greatly improved with dose-dependent telmisartan treatments.
  
  
  CONCLUSIONS
  These results suggest that telmisartan comprehensively protected the NVU components by reducing inflammatory reactions relative to AD in hypertensive rats, which could also preclude the risk of AD under hypertension.
authors.forename: Wentao
authors.initials: W
authors.lastname: Liu
authors.forename: Toru
authors.initials: T
authors.lastname: Yamashita
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kurata
authors.forename: Syoichiro
authors.initials: S
authors.lastname: Kono
authors.forename: Nozomi
authors.initials: N
authors.lastname: Hishikawa
authors.forename: Kentaro
authors.initials: K
authors.lastname: Deguchi
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhai
authors.forename: Koji
authors.initials: K
authors.lastname: Abe
mesh_terms: D000375:Aging / Q000187:drug effects / Q000378:metabolism; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D002352:Carrier Proteins / Q000378:metabolism; D002540:Cerebral Cortex / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism; D007150:Immunohistochemistry; D058847:Inflammasomes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D000069336:Neurovascular Coupling / Q000187:drug effects* / Q000502:physiology; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D000077333:Telmisartan
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000893:Anti-Inflammatory Agents; D001562:Benzimidazoles; D001565:Benzoates; D002352:Carrier Proteins; D005904:Glial Fibrillary Acidic Protein; D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C573346:Nlrp3 protein, rat; D003094:Collagen; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat; D000077333:Telmisartan
keywords: AD,; Hypertension,; Inflammasome,; Neurovascular unit,; SHR-SR,; Telmisartan