Telmisartan ameliorates inflammatory responses in SHR-SR after tMCAO

Kota Sato, Toru Yamashita, Tomoko Kurata, Yusuke Fukui, Nozomi Hishikawa, Kentaro Deguchi, Koji Abe

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Telmisartan, an angiotensin receptor blocker with high lipid solubility, also called metabo-sartan, not only reduces blood pressure (BP), but also ameliorates inflammation in the cerebral cortex and in adipose tissue. We examined the effects of telmisartan on inflammatory responses of monocyte chemotactic protein-1, tumor necrosis factor-a, and ionized calcium-binding adapter molecule 1 in the brain of spontaneously hypertensive rat stroke-resistant (SHR-SR) after transient middle cerebral artery occlusion (tMCAO). At 12 weeks of age, SHR-SR received tMCAO for 90 minutes and were divided into 3 groups, that is, the vehicle group, a low-dose telmisartan group (.3 mg/kg/day), and a high-dose telmisartan group (3 mg/kg/ day). Immunohistological analysis was performed when rats became 6, 12 and 18 months old. Monocyte chemotactic protein-1, tumor necrosis factor-a, and ionized calcium-binding adapter molecule 1 cells (/mm2) immunoreactivities increased with age in the cerebral cortex and hippocampus of the vehicle group, suggesting strong and persistent inflammatory changes in SHR-SR after tMCAO up to 18 months of age. On the other hand, a low dose of telmisartan significantly reduced such inflammatory changes without lowering BP, whereas a high dose of telmisartan showed a few additional improvements, including the lowering of BP throughout 6-18 months of age. The present study suggests that persistent hypertension after tMCAO caused a long-lasting inflammatory response in the SHR-SR brain, and that even a low dose of telmisartan reduced continuous inflammation without lowering BP via its pleiotropic effects in the SHR-SR brain. A high dose of telmisartan had a few additional benefits, including lowering BP.

Original languageEnglish
Pages (from-to)2511-2519
Number of pages9
JournalJournal of Stroke and Cerebrovascular Diseases
Volume23
Issue number10
DOIs
Publication statusPublished - 2014

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Middle Cerebral Artery Infarction
Inbred SHR Rats
Stroke
Blood Pressure
Chemokine CCL2
Cerebral Cortex
Brain
Tumor Necrosis Factor-alpha
Inflammation
Calcium
Angiotensin II Type 1 Receptor Blockers
telmisartan
Angiotensin Receptor Antagonists
Solubility
Adipose Tissue
Hippocampus
Hypertension
Lipids

Keywords

  • Iba-1
  • Inflammatory response
  • MCP, 1
  • Spontaneously hypertensive rat
  • Telmisartan
  • TNF
  • α

ASJC Scopus subject areas

  • Clinical Neurology
  • Surgery
  • Rehabilitation
  • Cardiology and Cardiovascular Medicine
  • Medicine(all)

Cite this

Telmisartan ameliorates inflammatory responses in SHR-SR after tMCAO. / Sato, Kota; Yamashita, Toru; Kurata, Tomoko; Fukui, Yusuke; Hishikawa, Nozomi; Deguchi, Kentaro; Abe, Koji.

In: Journal of Stroke and Cerebrovascular Diseases, Vol. 23, No. 10, 2014, p. 2511-2519.

Research output: Contribution to journalArticle

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