Telmisartan reduces progressive accumulation of cellular amyloid beta and phosphorylated tau with inflammatory responses in aged spontaneously hypertensive stroke resistant rat.

ABSTRACT

BACKGROUND: In addition to reducing the level of blood pressure (BP), telmisartan was expected to show the long-term neuroprotective effects preventing accumulation of cellular amyloid beta peptide (Aß) and phosphorylated tau (pτ) by ameliorating neuroinflammation. METHODS: We examined effects of telmisartan on cellular Aß and pτ with inflammatory responses in the brain of a spontaneously hypertensive stroke resistant (SHR-SR) rat by giving either telmisartan at 0 (vehicle), .3 mg/kg/day or 3 mg/kg/day, orally, from 3 months of age and performed immunohistologic analysis at 6, 12, and 18 months. Compared with normotensive Wistar rats, numbers of Aß- and pτ-positive neurons in the cerebral cortex progressively increased with age until 18 months in the SHR-SR rats, as did the numbers of ionized calcium-binding adapter molecule 1 (Iba-1)-positive microglia, tumor necrosis factor alpha (TNF-α)-positive neurons, and monocyte chemotactic protein 1 (MCP-1)-positive neurons. RESULTS: Low-dose telmisartan significantly decreased the numbers of Aß- and pτ-positive neuron as well as the numbers of TNF-α-positive neurons, Iba-1-positive microglia, and MCP-1-positive neurons at 6, 12, and 18 months. High-dose telmisartan reduced BP and showed a further reduction of cellular Aß and pτ. CONCLUSIONS: The present study suggests that accumulation of cellular Aß and pτ and the inflammatory responses were decreased via improving metabolic syndrome with low-dose telmisartan and improving both metabolic syndrome and hypertension with high-dose telmisartan.