title: Renoprotective effects of sildenafil in DOCA-salt hypertensive rats.
abstract: OBJECTIVE
  Sildenafil, the first selective phosphodiesterase-5 (PDE5) inhibitor to be widely used for treating erectile dysfunction, has been investigated with regard to its cardioand renoprotective effects in animal models. This study further investigated the renoprotective effects of sildenafil and their molecular mechanisms in deoxycorticosterone acetate (DOCA)-salt hypertensive (DSH) rats.
  
  
  METHODS
  DOCA strips (200 mg/kg) were implanted in rats 1 week after unilateral nephrectomy. These rats were fed on a control diet, with or without sildenafil (50 mg·kg(-1)day(-1)), for 2 weeks. Systolic blood pressure (SBP) was measured by the tail cuff method, and the urinary albumin-to-creatinine ratio (ACR) was calculated. The extent of glomerulosclerosis and tubulointerstitial fibrosis was determined by Masson's trichrome stain. Renal expression of ED-1, transforming growth factor-β1 (TGF-β1), Bax, and Bcl-2 were determined by semiquantitative immunoblotting, polymerase chain reaction (PCR), and immunohistochemistry. TUNEL staining was used for detecting apoptotic cells.
  
  
  RESULTS
  The increased SBP in DSH rats was not attenuated by sildenafil treatment. The decreased creatinine clearance and increased ACR in DSH rats, compared with control animals, were attenuated by sildenafil treatment. Further, sildenafil treatment attenuated glomerulosclerosis and tubulointerstitial fibrosis in DSH rats and counteracted the increased expression of ED-1, TGF-β1, and Bax and the decreased expression of Bcl-2 in the kidneys of these rats. The increase in the number of apoptotic cells in DSH rats was attenuated by sildenafil treatment.
  
  
  CONCLUSIONS
  Sildenafil effectively prevented the progression of renal injury in DSH rats via its anti-inflammatory, antifibrotic, and antiapoptotic effects.
authors.affiliation: Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Eun Hui
authors.initials: EH
authors.lastname: Bae
authors.forename: In Jin
authors.initials: IJ
authors.lastname: Kim
authors.forename: Soo Yeon
authors.initials: SY
authors.lastname: Joo
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Kim
authors.forename: Chang Seong
authors.initials: CS
authors.lastname: Kim
authors.forename: Joon Seok
authors.initials: JS
authors.lastname: Choi
authors.forename: Seong Kwon
authors.initials: SK
authors.lastname: Ma
authors.forename: Suhn Hee
authors.initials: SH
authors.lastname: Kim
authors.forename: Jong Un
authors.initials: JU
authors.lastname: Lee
authors.forename: Soo Wan
authors.initials: SW
authors.lastname: Kim
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D003900:Desoxycorticosterone / Q000009:adverse effects*; D004195:Disease Models, Animal; D018450:Disease Progression; D006973:Hypertension / Q000139:chemically induced* / Q000150:complications / Q000188:drug therapy*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D007674:Kidney Diseases / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011687:Purines / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000494:pharmacology / Q000627:therapeutic use*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494828:Bax protein, rat; D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D019253:Proto-Oncogene Proteins c-bcl-2; D011687:Purines; D013450:Sulfones; D053773:Transforming Growth Factor beta1; D051028:bcl-2-Associated X Protein; D003900:Desoxycorticosterone; D000068677:Sildenafil Citrate