Background: By acting on multiple targets and promoting diverse actions, angiotensin II
(Ang II) plays a pivotal role in vascular function. Recent studies suggested that phosphodiesterase-5
(PDE-5) inhibitors exhibit therapeutic effects in cardiovascular diseases. Here, the effects of sildenafil
on vascular disturbances were analyzed in a mouse model of Ang II-induced hypertension.
Methods and Results: Male C57BL/6 mice were used as untreated animals (control) or infused with
Ang II (1000 ηg/kg/min) for 28 days and treated with sildenafil (40 mg/kg/min) or vehicle (Ang II)
during the last two weeks. After 4 weeks, the Ang II animals exhibited a high systolic blood pressure
(186±3 mmHg vs. 127±3 mmHg for control mice), which was attenuated by sildenafil (163±7 mmHg).
The mesenteric vessels from the Ang II animals revealed damage to the endothelial layer, an increase
in the cross-section area (1.9-fold) and vascular cell production of peroxynitrite (512±13 a.u.), which
was ameliorated in the Ang II-Sil group (1.2-fold and 400±17 a.u.). Analysis of the vascular responsiveness
showed an increased contractility response to norepinephrine in Ang II animals (Rmax: 70%),
which was abolished by sildenafil through increased nitric oxide (NO) bioavailability and decreased
reactive oxygen species (ROS) and vasoconstrictor prostanoids.
Conclusion: Sildenafil attenuates the morphofunctional deleterious effects of Ang II on resistance vessels.
The benefits of sildenafil seem to occur through restoring the balance of ROS/NO/eicosanoids.
Therefore, this study opened new avenues for further clinical targeting of the treatment of cardiovascular
diseases related to activation of the renin-angiotensin system.