Telmisartan promotes potential glucose homeostasis in stroke-resistant spontaneously hypertensive rats via peroxisome proliferator-activated receptor γ activation.

Abstract

An angiotensin 2 type 1 receptor blocker (ARB) telmisartan possesses not only an anti-hypertensive 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.

• Authors: Yoshio Omote, Kentaro Deguchi, Tomoko Kurata, Toru Yamashita, Kota Sato, Nozomi Hishikawa, Koji Abe
• Journal: Current neurovascular research (Curr Neurovasc Res) Vol. 12 Issue 1 Pg. 91-7 ( 2015) ISSN: 1875-5739 [Electronic] United Arab Emirates
• PMID: 25557372 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiotensin II Type 1 Receptor Blockers
• Benzimidazoles
• Benzoates
• PPAR gamma
• Receptor, Angiotensin, Type 1
• Glucose
• Telmisartan

Topics

• Age Factors
• Angiotensin II Type 1 Receptor Blockers (therapeutic use)
• Animals
• Benzimidazoles (therapeutic use)
• Benzoates (therapeutic use)
• Disease Models, Animal
• Glucose (metabolism)
• Homeostasis (drug effects)
• Male
• PPAR gamma (metabolism)
• Rats
• Rats, Inbred SHR
• Rats, Wistar
• Receptor, Angiotensin, Type 1 (metabolism)
• Stroke (drug therapy)
• Telmisartan