Protective effect of telmisartan on neurovascular unit and inflammasome in stroke-resistant spontaneously hypertensive rats

Wentao Liu, Toru Yamashita, Tomoko Kurata, Syoichiro Kono, Nozomi Hishikawa, Kentaro Deguchi, Yun Zhai, Koji Abe

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Objectives: 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. Discussion: 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.

Original languageEnglish
Pages (from-to)491-501
Number of pages11
JournalNeurological Research
Volume37
Issue number6
DOIs
Publication statusPublished - May 1 2015

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Keywords

  • AD
  • Hypertension
  • Inflammasome
  • Neurovascular unit
  • SHR-SR
  • Telmisartan

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

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