Sildenafil restores endothelial function and reduces blood pressure in experimental hypertension

Abstract

The aim of this study was to evaluate the effects of sildenafil on endothelial function of hypertensive mice. Male C57BL/6 mice (n=3–10) were subjected to renal artery clipping (2K1C). After 14 days, sildenafil (40 mg/kg/day) or vehicle was administrated for 14 days. At the end of the treatment, mice were anesthetized and catheterized to blood pressure recording and had the mesenteric arteriolar bed (MAB) and thoracic aorta (TA) removed to vascular function studies. Data are mean ± SEM. One‐way ANOVA was performed followed by Tukey's post hoc test. Sildenafil caused a significant reduction in the arterial blood pressure in treated mice (126±3 vs. 110±4mmHg). Endothelial dysfunction was observed in MAB of 2K1C mice, but not in the TA and it was restored by sildenafil (Rmax ACh: 44±2.6% vs. 59±4.5%). Ongoing studies are revealing an augmented participation of nitric oxide in this process in treated animals. Similarly, an increased maximal response to an alpha 1‐agonist was observed in MAB but not in TA in 2K1C mice, which was ameliorated by sildenafil (167±8 vs.117±9 mmHg). Both TA and MAB did not show impairment in smooth vascular relaxation to sodium nitroprusside. Thus, our data showed that sildenafil can restore endothelial function in hypertensive mice, which reflects in a significant reduction of arterial hypertension.Financial Support: CNPq (Proc. 302582/2011–8) and FAPES/Universal 012/2011 (Proc. 54498465).