title: Inhibition of phosphodiesterase 5 restores endothelial function in renovascular hypertension.
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 (~35% and ~140%) compared with the Sham mice. Sildenafil normalized the intrarenal Ang I and II and increased the plasma (~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.
  
  
  CONCLUSIONS
  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.
authors.forename: Ananda T
authors.initials: AT
authors.lastname: Dias
authors.forename: Amanda S
authors.initials: AS
authors.lastname: Cintra
authors.forename: Jéssica C
authors.initials: JC
authors.lastname: Frossard
authors.forename: Zaira
authors.initials: Z
authors.lastname: Palomino
authors.forename: Dulce E
authors.initials: DE
authors.lastname: Casarini
authors.forename: Isabele B S
authors.initials: IB
authors.lastname: Gomes
authors.forename: Camille M
authors.initials: CM
authors.lastname: Balarini
authors.forename: Agata L
authors.initials: AL
authors.lastname: Gava
authors.forename: Bianca P
authors.initials: BP
authors.lastname: Campagnaro
authors.forename: Thiago M C
authors.initials: TM
authors.lastname: Pereira
authors.forename: Silvana S
authors.initials: SS
authors.lastname: Meyrelles
authors.forename: Elisardo C
authors.initials: EC
authors.lastname: Vasquez
mesh_terms: D000809:Angiotensins / Q000097:blood; D000818:Animals; D001794:Blood Pressure; D001835:Body Weight; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5 / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005434:Flow Cytometry; D006339:Heart Rate; D006978:Hypertension, Renovascular / Q000201:enzymology / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size; D018384:Oxidative Stress; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology*
chemical_list: D000809:Angiotensins; D058986:Phosphodiesterase 5 Inhibitors; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5