title: The effects of sildenafil citrate on uterine angiogenic status and serum inflammatory markers in an L-NAME rat model of pre-eclampsia.
abstract: Pre-eclampsia (PE), a hypertensive disorder of pregnancy, is detrimental to both mother and foetus. There is currently no effective treatment, but we have shown that Sildenafil Citrate (SC) improve various foetal outcomes in Nω-nitro-L arginine methyl ester (L-NAME) rat model of PE. Therefore, we aimed to investigate the effects of SC on a uterine angiogenic status and serum inflammatory markers in an L-NAME rat model of PE. One hundred and twenty adult nulliparous pregnant female Sprague-Dawley rats were used for the study. These were divided into five equal groups; the pregnant control, early and late onset PE and respective SC treated animals. Hypertension was manifested by considerably increased systolic blood pressure and placental lipid peroxidative marker (thiobarbituric acid reactive substances) and also we assessed the activities of plasma nitric oxide level, serum inflammatory marker (TGF-β and IFN-γ) and uterine angiogenic status (VEGF and sFlt-1) at two stages of PE. The administration of SC decreased systolic blood pressure, placental lipid peroxidation product and altered uterine angiogenic status; increased plasma nitric oxide levels in an early and late onset L-NAME model of PE. In addition, histological findings of SC treated preeclamptic rat placenta support the biochemical findings of this study. Our findings revealed that SC enhanced plasma NO levels and uterine angiogenic status in an L-NAME model of PE at two gestational stages.
authors.affiliation: Department of Human Physiology, School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa.
authors.forename: Nerolen
authors.initials: N
authors.lastname: Soobryan
authors.affiliation: Department of Human Physiology, School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa. Electronic address: murugesans@ukzn.ac.za.
authors.forename: Saravanakumar
authors.initials: S
authors.lastname: Murugesan
authors.affiliation: Department of Human Physiology, School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa.
authors.forename: Wendy
authors.initials: W
authors.lastname: Phoswa
authors.affiliation: Department of Family Medicine, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.
authors.forename: Prem
authors.initials: P
authors.lastname: Gathiram
authors.affiliation: Department of Obstetrics and Gynaecology and Women's Health and HIV Research Unit, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.
authors.forename: Jagidesa
authors.initials: J
authors.lastname: Moodley
authors.affiliation: Department of Human Physiology, School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa. Electronic address: mackraji@ukzn.ac.za.
authors.forename: Irene
authors.initials: I
authors.lastname: Mackraj
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007249:Inflammation / Q000097:blood; D007371:Interferon-gamma / Q000097:blood; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D009569:Nitric Oxide / Q000097:blood; D011225:Pre-Eclampsia / Q000097:blood* / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000068677:Sildenafil Citrate / Q000494:pharmacology* / Q000627:therapeutic use; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000097:blood; D014599:Uterus / Q000187:drug effects* / Q000503:physiopathology*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; D009569:Nitric Oxide; D007371:Interferon-gamma; D000068677:Sildenafil Citrate; D040281:Vascular Endothelial Growth Factor Receptor-1; D019331:NG-Nitroarginine Methyl Ester
keywords: Nitric oxide; Pre-eclampsia; Sildenafil citrate; Soluble fms-like tyrosine kinase-1