The effects of sildenafil citrate on urinary podocin and nephrin mRNA expression in an l-NAME model of pre-eclampsia

• Published in: Molecular and cellular biochemistry 2017-03, Vol.427 (1-2), p.59-67
• Main Authors: Baijnath, Sooraj, Murugesan, Saravanakumar, Mackraj, Irene, Gathiram, Prem, Moodley, Jagidesa
• Format: Article
• Language: English
• Subjects: Animal models; Animals; Biochemistry; Biomedical and Life Sciences; Blood pressure; Cardiology; Clinical outcomes; Comparative analysis; Disease Models, Animal; Drinking water; Drug therapy; Female; Gene Expression Regulation - drug effects; Humans; Intracellular Signaling Peptides and Proteins - urine; Kidney - metabolism; Kidney - pathology; Life Sciences; Light microscopy; Medical Biochemistry; Membrane Proteins - urine; NG-Nitroarginine Methyl Ester - adverse effects; NG-Nitroarginine Methyl Ester - pharmacology; Oncology; Pre-Eclampsia - chemically induced; Pre-Eclampsia - drug therapy; Pre-Eclampsia - pathology; Pre-Eclampsia - urine; Preeclampsia; Pregnancy; Prescription drugs; Rats; Rats, Sprague-Dawley; RNA, Messenger - biosynthesis; Sildenafil Citrate - pharmacology; Vascular endothelial growth factor
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1007/s11010-016-2897-5

We investigated the effects of sildenafil citrate (SC) on podocyturia in N ω -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.