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Current Neurovascular Research

Eiditor-in-Chief

ISSN (Print): 1567-2026
ISSN (Online): 1875-5739

Telmisartan Promotes Potential Glucose Homeostasis in Stroke-Resistant Spontaneously Hypertensive Rats via Peroxisome Proliferator-Activated Receptor γ Activation

Author(s): Yoshio Omote, Kentaro Deguchi, Tomoko Kurata, Toru Yamashita, Kota Sato, Nozomi Hishikawa and Koji Abe

Volume 12 , Issue 1 , 2015

Page: [91 - 97] Pages: 7

DOI: 10.2174/1567202612666150104150310

Price: $58

Abstract

An angiotensin 2 type 1 receptor blocker (ARB) telmisartan possesses not only an antihypertensive effect but also an anti-metabolic syndrome effect due to peroxisome proliferator-activated receptor γ (PPAR-γ) activation. In the present study, we examined the effects of telmisartan on the angiotensin 2 type 1 receptor (AT1R), PPAR-γ, and insulin receptor (IR) in stroke-resistant spontaneously hypertensive rats (SHR-SR), comparing them with Wistar rats. Three-months-old SHR-SR rats were divided into three treatment groups, i.e., vehicle (SHR/Ve), low-dose telmisartan (0.3 mg/kg/day, SHR/Low), and high-dose telmisartan (3 mg/kg/day, SHR/High). Compared with Wistar rats, SHR/Ve increased the staining of AT1R, PPAR-γ and IR in the cerebral cortical neurons. On the other hand, telmisartan dose-dependently suppressed the excessive expression of AT1R and IR, but enhanced PPAR-γ activation. Low-dose telmisartan showed these effects even without lowering blood pressure (BP), while high-dose telmisartan lowered BP and showed further effects. The present study suggests that even a low dose of telmisartan decreased AT1R and IR, and increased PPAR-γ in the cerebral cortex of SHR-SR without lowering BP, probably by improving glucose homeostasis. The high dose of telmisartan showed further decreases in AT1R and IR, and further PPAR-γ activation while lowering BP, suggesting an additive benefit to lowering BP, namely the improvement of glucose homeostasis.

Keywords: Telmisartan, SHR-SR, AT1R, PPAR-γ, insulin receptor 3.


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