Telmisartan inhibits cytokine-induced nuclear factor-κB activation independently of the peroxisome proliferator-activated receptor-γ

Telmisartan is an angiotensin-II type 1 receptor (AT1R) blocker, currently used to treat patients with hypertension. Telmisartan, in addition to its effect on AT1R, is thought to activate the nuclear transcription factor, peroxisome proliferator-activated receptor-gamma (PPAR gamma), thereby acting as a partial PPAR gamma agonist. This study was conducted to examine whether telmisartan might suppress cytokine-induced inflammatory signaling in vascular endothelial cells, thereby attenuating cellular inflammation possibly by PPAR gamma activation. Telmisartan caused a dose-dependent suppression of the tumor necrosis factor-alpha (TNF alpha)-induced activation of nuclear factor (NF)-kappa B in vascular endothelial cells in this study. The PPAR gamma antagonist, GW9662, did not influence the inhibitory effect of telmisartan on NF-kappa B activation. The thiazolidinediones neither influenced TNF alpha-induced NF-kappa B activation nor influenced the inhibitory effect of telmisartan in this process. Telmisartan dose dependently diminished the TNF alpha-induced gene expression of VCAM-1, and GW9662 did not attenuate this effect. Thus, telmisartan inhibits the cytokine-induced expression of the VCAM-1 gene by blocking NF-kappa B activation independently of PPAR gamma activation. Although the mechanism by which this occurs remains unclear, our findings suggest that telmisartan-induced anti-inflammatory effects might have favorable effects on vasculature in hypertensive patients. Hypertension Research (2009) 32, 765-769; doi: 10.1038/hr.2009.95; published online 10 July 2009