Telmisartan prevents angiotensin II-induced endothelial dysfunction in rabbit aorta via activating HGF/Met system and PPARγ pathway.

Telmisartan with partial activation of peroxisome proliferator-activated receptor γ (PPARγ) powerfully reduces blood pressure, improves endothelial function and lipid metabolism. Hepatocyte growth factor/mesenchymal-epithelial transition factor (HGF/Met) system in the local vasculature plays a pivotal role in maintaining normal endothelial function. This study is aimed to evaluate whether telmisartan directly prevents angiotensin II (Ang II)-induced endothelial dysfunction (ED) via activating HGF/Met system and/or PPARγ pathway. The isolated aortic rings of rabbits were incubated with Ang II (0.01-1 μM), telmisartan (0.1-10 μM), SU11274 (5 μM) as a specific Met inhibitor, GW9662 (10 μM) as a PPARγ antagonist alone or a combination for 6 h. Ang II obviously inhibited the mRNA and protein expression of HGF, Met and PPARγ, and the accumulative concentration-relaxation of the aortic rings to acetylcholine, among which the inhibitory effect of 1 μM Ang II was most significant. By contrast, telmisartan significantly increased the mRNA and protein expression of HGF, Met, and PPARγ, thus preventing Ang II-induced ED in a dose-dependent pattern. However, SU11274, GW9662 or a combination of both partially abolished the protective effects derived from telmisartan, with the effect of SU11274 exceeding that of GW9662. These results demonstrate that Ang II-induced ED in rabbit aortic rings in vitro can be prevented by telmisartan through selective PPARγ-modulating pathway. Moreover, this study indicates for the first time that activating HGF/Met system in the local vasculature is involved in the protective mechanism of telmisartan.