Abstract

In translational medicine, the discovery of new drugs or new potential uses for currently available drugs is crucial for treating the resistant hypertension associated with renal artery stenosis. The phosphodiesterase 5 inhibitor sildenafil has been shown to reduce blood pressure and to improve the endothelium-dependent relaxation in the two kidney, one clip (2K1C) mouse model of renovascular hypertension. In the present study, we evaluated the effects of sildenafil (40 mg/kg/day for two weeks) on the endothelial structure and contractile function in mesenteric resistance arteries 28 days after clipping the renal artery. The data showed an enhanced vascular contractile response to norepinephrine in 2K1C hypertensive mice (56%) when compared with Sham mice, which was associated with increased oxidative stress and with a thinning of endothelial cells. Sildenafil treatment caused a significant amelioration in the enhanced contractile responsiveness (18%), which was associated to the recovery of the endothelial surface and abolishment of the oxidative stress. These data suggest that sildenafil could be considered a promising therapeutic option to manage endothelial dysfunction and hypertension in resistant patients.

Keywords: 2K1C, endothelial cells, endothelial dysfunction, renovascular hypertension, resistance arteries, sildenafil.