title: The effects of sildenafil citrate on urinary podocin and nephrin mRNA expression in an L-NAME model of pre-eclampsia.
abstract: We investigated the effects of sildenafil citrate (SC) on podocyturia in Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME) model of pre-eclampsia (PE). One hundred and twenty Sprague-Dawley rats (SDR) were divided into five groups like pregnant control (PC), early-onset PE (EOPE), late-onset PE(LOPE), early and late-onset PE with SC-treated groups [EOPE (SC); LOPE (SC)]. PE was induced in SDR by oral administration of L-NAME in drinking water for 4-8 days for EOPE and 8-14 day for LOPE. The blood pressure, urine volume and total urine protein were increased in EOPE and LOPE groups when compared to PC, and all the above parameters decreased in EOPE (SC) and LOPE (SC) groups when compared to EOPE and LOPE groups, respectively. The EOPE and LOPE groups showed an increase in urinary nephrin mRNA and podocin mRNA levels compared to PC group. Increases in serum and renal soluble fms-like tyrosine kinase-1 (sFlt-1) expression levels and decreases in renal vascular endothelial growth factor (VEGF) expression and serum placenta growth factor (PlGF) levels were observed in EOPE and LOPE groups when compared to PC group. In addition, decreases in serum and renal sFlt-1 expression levels and increases in renal VEGF expression and serum PlGF levels were observed in EOPE (SC) and LOPE (SC) groups when compared to EOPE and LOPE groups, respectively. The light microscopy showed that the renal tissue of L-NAME-treated rats had extensive glomerular damage, tubular damage and infiltration by mononuclear cells when compared to PC group. Therefore, SC ameliorated podocyturia through its effects on the antiangiogenic/angiogenic status in this animal model.
authors.affiliation: Department of Human Physiology, School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa.
authors.forename: Sooraj
authors.initials: S
authors.lastname: Baijnath
authors.affiliation: Department of Human Physiology, School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa. 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. mackraji@ukzn.ac.za.
authors.forename: Irene
authors.initials: I
authors.lastname: Mackraj
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 Group, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.
authors.forename: Jagidesa
authors.initials: J
authors.lastname: Moodley
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000652:urine*; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins / Q000652:urine*; D019331:NG-Nitroarginine Methyl Ester / Q000009:adverse effects* / Q000494:pharmacology; D011225:Pre-Eclampsia / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology / Q000652:urine; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000068677:Sildenafil Citrate / Q000494:pharmacology*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C407223:NPHS2 protein; D012333:RNA, Messenger; C113267:nephrin; D000068677:Sildenafil Citrate; D019331:NG-Nitroarginine Methyl Ester
keywords: PlGF; Podocyturia; Pre-eclampsia; Sildenafil citrate; sFlt-1