Beneficial Morphofunctional Changes Promoted by Sildenafil in Resistance Vessels in the Angiotensin II-Induced Hypertension Model.

Abstract

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.

• Authors: Ananda T Dias, Marcos A S Leal, Tadeu C Zanardo, Gisele M Alves, Marcella L Porto, Breno V Nogueira, Agata L Gava, Bianca P Campagnaro, Thiago M C Pereira, Silvana S Meyrelles, Manuel Campos-Toimil, Elisardo C Vasquez
• Journal: Current pharmaceutical biotechnology (Curr Pharm Biotechnol) Vol. 19 Issue 6 Pg. 483-494 ( 2018) ISSN: 1873-4316 [Electronic] Netherlands
• PMID: 29938618 (Publication Type: Journal Article)
• Copyright: Copyright© Bentham Science Publishers; For any queries, please email at [email protected].

Chemical References

• Phosphodiesterase 5 Inhibitors
• Reactive Oxygen Species
• Angiotensin II
• Sildenafil Citrate

Topics

• Angiotensin II (pharmacology)
• Animals
• Hypertension (chemically induced, drug therapy, physiopathology)
• Male
• Mesenteric Arteries (drug effects, physiopathology)
• Mice
• Mice, Inbred C57BL
• Phosphodiesterase 5 Inhibitors (pharmacology)
• Reactive Oxygen Species (metabolism)
• Sildenafil Citrate (pharmacology)