Inhibition of phosphodiesterase 5 restores endothelial function in renovascular hypertension

Inhibition of phosphodiesterase 5 restores endothelial function in renovascular hypertension

Author Dias, Ananda T. Google Scholar
Cintra, Amanda S. Google Scholar
Frossard, Jessica C. Google Scholar
Palomino, Zaira Autor UNIFESP Google Scholar
Casarini, Dulce Elena Autor UNIFESP Google Scholar
Gomes, Isabele B. S. Google Scholar
Balarini, Camille M. Google Scholar
Gava, Agata L. Google Scholar
Campagnaro, Bianca P. Google Scholar
Pereira, Thiago M. C. Google Scholar
Meyrelles, Silvana S. Google Scholar
Vasquez, Elisardo C. Google Scholar
Institution Univ Fed Espirito Santo
Emescam Sch Hlth Sci
Universidade Federal de São Paulo (UNIFESP)
Univ Fed Paraiba
Fed Inst Educ Sci & Technol IFES
Abstract Background: the clipping of an artery supplying one of the two kidneys (2K1C) activates the renin-angiotensin (Ang) system (RAS), resulting in hypertension and endothelial dysfunction. Recently, we demonstrated the intrarenal beneficial effects of sildenafil on the high levels of Ang II and reactive oxygen species (ROS) and on high blood pressure (BP) in 2K1C mice. Thus, in the present study, we tested the hypothesis that sildenafil improves endothelial function in hypertensive 2K1C mice by improving the NO/ROS balance.Methods: 2K1C hypertension was induced in C57BL/6 mice. Two weeks later, they were treated with sildenafil (40 mg/kg/day, via oral) or vehicle for 2 weeks and compared with sham mice. At the end of the treatment, the levels of plasma and intrarenal Ang peptides were measured. Endothelial function and ROS production were assessed in mesenteric arterial bed (MAB).Results: the 2K1C mice exhibited normal plasma levels of Ang I, II and 1-7, whereas the intrarenal Ang I and II were increased (similar to 35% and similar to 140%) compared with the Sham mice. Sildenafil normalized the intrarenal Ang I and II and increased the plasma (similar to 45%) and intrarenal (+15%) Ang 1-7. the 2K1C mice exhibited endothelial dysfunction, primarily due to increased ROS and decreased NO productions by endothelial cells, which were ameliorated by treatment with sildenafil.Conclusion: These data suggest that the effects of sildenafil on endothelial dysfunction in 2K1C mice may be due to interaction with RAS and restoring NO/ROS balance in the endothelial cells from MAB. Thus, sildenafil is a promising candidate drug for the treatment of hypertension accompanied by endothelial dysfunction and kidney disease.
Keywords Sildenafil
Oxidative stress
Renovascular hypertension
Endothelial function
Language English
Sponsor Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
State Agency for the Development of Science and Technology (FAPES/Universal)
Grant number CNPq: 302582/2011-8
CNPq: 476525/2012-8
CNPq: 305188/2012-7
CNPq: 473177/2013-7
State Agency for the Development of Science and Technology (FAPES/Universal): 012/2011
State Agency for the Development of Science and Technology (FAPES/Universal): 54498465
CNPq: 012/2009
Date 2014-09-16
Published in Journal of Translational Medicine. London: Biomed Central Ltd, v. 12, 14 p., 2014.
ISSN 1479-5876 (Sherpa/Romeo, impact factor)
Publisher Biomed Central Ltd
Extent 14
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000342174600001

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