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

Abstract

ObjectivesWe 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 designThis 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. ResultsThere was a significant increase in the plasma levels of soluble fms-like tyrosine kinase1 (sFlt-1) in the PRE group (1228.80±116.29pg/ml) when compared to the CON (774.91±26.81pg/ml) and SCT (698.98±20.78pg/ml) groups, respectively (p<0.001). The plasma levels of soluble endoglin (sEng) were significantly decreased in the SCT group (149.47±3.72ng/ml) when compared to the CON (178.52±5.33ng/ml) and PRE (183.44±8.294ng/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. ConclusionSildenafil 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.