Sildenafil citrate decreases sFlt-1 and sEng in pregnant L-NAME treated Sprague-Dawley rats

Objectives: 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. Study design: 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. Conclusion: 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. (C) 2011 Elsevier Ireland Ltd. All rights reserved.