title: Sildenafil treatment prevents glomerular hypertension and hyperfiltration in rats with renal ablation.
abstract: BACKGROUND
  Sildenafil treatment ameliorates progressive renal injury resulting from extensive renal ablation; however, modifications induced by sildenafil in the glomerular hemodynamic pathophysiology of the remnant kidney have not been investigated.
  
  
  OBJECTIVE
  To determine the effects of sildenafil in the glomerular microcirculation and their relation to histological damage in the renal ablation model.
  
  
  METHODS
  Micropuncture studies were performed 60 days after 5/6 nephrectomy in rats that received no treatment, sildenafil (5 mg/kg/day) and reserpine, hydralazine and hydrochlorothiazide to maintain the blood pressure within normal levels. Sham-operated rats untreated and treated with sildenafil served as controls.
  
  
  RESULTS
  As expected, renal ablation induced systemic and glomerular hypertension, hyperfiltration, proteinuria, glomerulosclerosis and tubulointerstitial inflammatory damage in the remnant kidney. Sildenafil treatment prevented single-nephron hyperfiltration and hypertension, suppressed renal arteriolar remodeling, ameliorated systemic hypertension and proteinuria, increased urinary excretion of cGMP and NO(2)(-)/NO(3)(-), decreased oxidative stress and improved histological damage in the remnant kidney. Normalization blood pressure with reserpine, hydralazine and hydrochlorothiazide did not modify glomerular hemodynamics, proteinuria or histological changes induced by renal ablation.
  
  
  CONCLUSIONS
  Beneficial effects of sildenafil in the remnant kidney are associated with a reduction in the arteriolar remodeling, renal inflammatory changes and prevention of changes in the glomerular microcirculation.
authors.affiliation: Department of Nephrology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico.
authors.forename: Edilia
authors.initials: E
authors.lastname: Tapia
authors.forename: Laura G
authors.initials: LG
authors.lastname: Sanchez-Lozada
authors.forename: Virgilia
authors.initials: V
authors.lastname: Soto
authors.forename: Andrés M
authors.initials: AM
authors.lastname: Manrique
authors.forename: Karla M
authors.initials: KM
authors.lastname: Ortiz-Vega
authors.forename: José
authors.initials: J
authors.lastname: Santamaría
authors.forename: Omar N
authors.initials: ON
authors.lastname: Medina-Campos
authors.forename: Magdalena
authors.initials: M
authors.lastname: Cristóbal
authors.forename: Carmen
authors.initials: C
authors.lastname: Avila-Casado
authors.forename: José
authors.initials: J
authors.lastname: Pedraza-Chaverri
authors.forename: Bernardo
authors.initials: B
authors.lastname: Rodríguez-Iturbe
authors.forename: Martha
authors.initials: M
authors.lastname: Franco
mesh_terms: D000818:Animals; D006973:Hypertension / Q000473:pathology / Q000517:prevention & control* / Q000601:surgery*; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000473:pathology / Q000601:surgery*; D008297:Male; D009392:Nephrectomy; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use*; D011687:Purines / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate