title: Effects of sildenafil and tadalafil on intraocular pressure in sheep: implications for aqueous humor dynamics.
abstract: OBJECTIVE
  To determine the effects of vasodilators on intraocular pressure (IOP) and the protein content of sheep aqueous humor (AH), because the vasodilators may increase fluid leakage from the fenestrated capillaries of the ciliary body to the extracellular tissue and directly to the anterior chamber (AC) via the iris, and some senior patients (older than 70) treated with sildenafil have exhibited elevated IOP.
  
  
  METHODS
  Experiments were performed on domestic sheep residing on a ranch in Argentina. These docile and compliant animals readily swallowed tablets of sildenafil (50 and 100 mg) and tadalafil (20 mg). IOP was monitored by Perkins applanation tonometry in 21 normal sheep receiving orally administered drugs. In addition, paracentesis was performed on six sheep to quantify changes in AH protein levels.
  
  
  RESULTS
  Ingestion of both sildenafil and tadalafil increased sheep IOP from normal levels of approximately 9 to 11 mm Hg within 1 hour. The IOP elevation was approximately 1.6-fold with both doses of sildenafil. IOP returned to control values within 4 hours. With the longer-lasting vasodilator tadalafil, IOP remained 1.6- to 1.9-fold higher than normal for at least 48 hours and returned to control levels within 4 days. The AH protein content was approximately 39% higher in sheep given 100 mg sildenafil.
  
  
  CONCLUSIONS
  These data are consistent with a vasodilator-evoked increase in plasma-like fluid in the AC, which likely accounts for the IOP elevation. The results are discussed with a model for AH dynamics that may be of importance to senior individuals treated for vascular diseases with these compounds.
authors.affiliation: Departamento de Oftalmología, Facultad de Medicina, Universidad Nacional Del Nordeste, Corrientes, Argentina.
authors.forename: Rosana
authors.initials: R
authors.lastname: Gerometta
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Alvarez
authors.forename: Oscar A
authors.initials: OA
authors.lastname: Candia
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism*; D002243:Carbolines / Q000008:administration & dosage*; D005260:Female; D007429:Intraocular Pressure / Q000187:drug effects*; D008297:Male; D010879:Piperazines / Q000008:administration & dosage*; D011687:Purines / Q000008:administration & dosage; D012756:Sheep; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000008:administration & dosage*; D000068581:Tadalafil; D014065:Tonometry, Ocular; D014665:Vasodilator Agents / Q000008:administration & dosage*
chemical_list: D002243:Carbolines; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D000068581:Tadalafil; D000068677:Sildenafil Citrate