title: Sildenafil citrate decreases sFlt-1 and sEng in pregnant l-NAME treated Sprague-Dawley rats.
abstract: OBJECTIVE
  We have previously shown that sildenafil citrate improves various fetal outcomes in pregnant, L-NAME treated, Sprague-Dawley rats. We therefore aimed to identify which component/s of this diverse pathophysiologic cascade is/are improved by this drug.
  
  
  METHODS
  This study is a sub-analysis of plasma samples obtained in a previous study in which 24 pregnant Sprague-Dawley dams were divided into three groups (n=8) i.e. the control group (CON), the experimental control group (PRE) where the pre-eclampsia-like symptoms were induced using l-NAME, and the experimental group (SCT) where the pre-eclampsia-like symptoms were once again induced using L-NAME but these animals were treated with sildenafil citrate. On gestation day 20 blood samples were collected in heparin-coated tubes and plasma samples were then analysed for specific variables using commercially available kits for rats.
  
  
  RESULTS
  There was a significant increase in the plasma levels of soluble fms-like tyrosine kinase1 (sFlt-1) in the PRE group (1228.80±116.29 pg/ml) when compared to the CON (774.91±26.81 pg/ml) and SCT (698.98±20.78 pg/ml) groups, respectively (p<0.001). The plasma levels of soluble endoglin (sEng) were significantly decreased in the SCT group (149.47±3.72 ng/ml) when compared to the CON (178.52±5.33 ng/ml) and PRE (183.44±8.294 ng/ml) groups, respectively (p<0.01). Plasma nitric oxide and l-arginine levels showed a decreasing trend in the PRE groups when compared to the control (CON) and treated (SCT) groups, respectively.
  
  
  CONCLUSIONS
  Sildenafil citrate reduces the plasma levels of anti-angiogenic factors, sFlt-1 and sEng, in pre-eclamptic (L-NAME induced) Sprague-Dawley rats and may therefore be responsible for the reduction in blood pressure and proteinuria as well as the improved fetal outcomes noted in an earlier study.
authors.affiliation: Department of Physiology and Physiological Chemistry, University of Kwa Zulu-Natal, Durban, South Africa. shamal.ramesar@yahoo.com
authors.forename: S V
authors.initials: SV
authors.lastname: Ramesar
authors.forename: I
authors.initials: I
authors.lastname: Mackraj
authors.forename: P
authors.initials: P
authors.lastname: Gathiram
authors.forename: J
authors.initials: J
authors.lastname: Moodley
mesh_terms: D000818:Animals; D001120:Arginine / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D000071063:Endoglin; D005260:Female; D047908:Intracellular Signaling Peptides and Proteins / Q000097:blood* / Q000187:drug effects; D023421:Models, Animal; D019331:NG-Nitroarginine Methyl Ester / Q000009:adverse effects*; D009569:Nitric Oxide / Q000097:blood; D010879:Piperazines / Q000494:pharmacology* / Q000627:therapeutic use; D011225:Pre-Eclampsia / Q000097:blood* / Q000139:chemically induced* / Q000188:drug therapy; D011247:Pregnancy; D011256:Pregnancy Outcome; D011270:Pregnancy, Animal / Q000097:blood* / Q000187:drug effects; D011687:Purines / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000494:pharmacology* / Q000627:therapeutic use; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood* / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000071063:Endoglin; C501740:Eng protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D009569:Nitric Oxide; D001120:Arginine; D000068677:Sildenafil Citrate; C501164:Flt1 protein, rat; D040281:Vascular Endothelial Growth Factor Receptor-1; D019331:NG-Nitroarginine Methyl Ester