The optimisation of a preeclampsia-like L-NAME rat model : a focus on utero-placental dysfunction.
Preeclampsia is a multi-system pregnancy syndrome characterized by the sudden onset of hypertension, escalated proteinuria and in some cases oedema usually after 20 weeks of gestation. Preeclampsia is further categorized as a two stage disorder namely; early and late onset. This study was aimed at developing a rat model that will mimic the classic clinical symptoms in preeclampsia through chronic administration of Nitro–L-Arginine Methyl Ester (L-NAME), and investigated whether Sildenafil Citrate (ViagraTM) (SC) aided in alleviating these symptoms. One hundred and twenty adult nulliparous pregnant female Sprague Dawley rats were used for the study. These were divided into five groups; the pregnant control, early and late onset and respective ViagraTM treated animals. On gestational day 12 and 19 as well as after delivery, physiological parameters such as blood pressure, proteinuria, urine volume, foetal body weight and number of live pups were taken. Post sacrifice and tissue harvesting, various histological, biochemical and gene expression analyses were done. The identification of probable early and late onset biomarkers to characterize preeclampsia was investigated (Ethics number: 047/12/Animal). We found that the administration of L-NAME during the pregnancy created a preeclamptic like syndrome. SC treated rats showed improved foetal and maternal parameters compared to their respective preeclamptic group. The results of this study support angiogenic, antiangiogenic and inflammatory markers as possible biomarkers for preeclampsia. Further studies using our model and in vitro studies, can help to clarify key questions; such as when exactly does remodelling of the spiral arteries occur, as well as the early detection of this disorder. This study which focuses on the optimisation of an animal model is of great interest to clinicians who do not have a biomarker for the early onset of preeclampsia.