Sildenafil improves cardiovascular function in experimental hypertension (676.5)

Abstract

The aim of the present study was to evaluate the beneficial cardiovascular effects of sildenafil treatment on experimental hypertension. Male C57BL/6 mice (n=5‐10) were subjected to 2K1C hypertension. After 14 days, sildenafil (40 mg/kg/day) or vehicle was administrated, during a period of 14 days. At the end of experimental period, animals were anesthetized and catheterized to blood pressure recording and had the mesenteric arteriolar bed removed to vascular function studies (acetylcholine ‐ ACh and norephrine ‐ Nor curves) (Protocol 02/2013‐ CEUA‐EMESCAM). Data are mean ± SEM. One‐way ANOVA was performed, followed by Tukey's post hoc test.*p<0.05 and **p<0.01 vs. 2K1C + vehicle. Sildenafil treatment reduced mean arterial blood pressure (124±2 vs. 112±3* mmHg) and heart rate (577±32 vs. 472±19* bpm) in hypertensive‐treated animals. Endothelial function was impaired in hypertensive animals and was successfully restored by sildenafil (Rmax ACh: 50.5±2% vs. 71.6±3%**). Blockage of nitric oxide production with L‐NAME revealed that the participation of this molecule in ACh‐induced vasodilation was augmented by sildenafil (AUC: 60.6±8 vs. 126.8±24*). Similarly, blockage with indomethacin showed the increased participation of COX‐derived prostanoids in vasodilation of treated animals (AUC: 37.9±9 vs. 95.9±17*). The participation of reactive oxygen species was evaluated by blockage of NADPH oxidase with apocinin and revealed that sildenafil was efficient in reducing oxidative stress (AUC: 94.±7.3 vs. 47.4±10.4*). Furthermore, sildenafil was also successful in reducing hyperactivity to Nor in 2K1C animals (Rmax: 167±8 vs. 117±9** mmHg). Thus, sildenafil can restore endothelial function and reduce blood pressure in experimental hypertension and could be suggested as a novel therapeutic approach while treating hypertensive patients. Grant Funding Source: Supported by: Fapes 54498465; CNPq 476525/2012‐8, 473082/2013‐6; FAPES/CNPq/PRONEX Edital 012/2009