Abstract 12160: Ascorbate Prevents Hypertension, Proteinuria and Concentric Hypertrophy in a Model of Preeclampsia, The S-Nitrosoglutathione Reductase (GSNOR) Deficient Mouse
Introduction: Preeclampsia is characterized by increased levels of S-nitrosylated protein and decreased levels of ascorbate (Asc), which is required for the release of nitric oxide (NO) from nitrosylated protein, suggesting that reduced NO bioavailability contributes to this syndrome. Increased levels of S-nitroyslated proteins are present in mice lacking S-nitrosoglutathione reductase (GSNOR), a denitrosylase that regulates S-nitrosylation, and these mice exhibit the phenotype of preeclampsia with pregnancy-induced hypertension (PIH), proteinuria, concentric hypertrophy and fetal growth restriction. In this study, we tested the hypothesis that the pathological features of preeclampsia in the GSNOR–/– can be rescued with ascorbate.
Methods: Pregnant GSNOR–/– and control mice (N=5-7) were studied at a late stage of pregnancy (17.5d). Ascorbate was given in drinking water starting at day 0.5. Proteinuria was determined using a dipstick, blood pressure was determined using a Millar catheter, and left ventricular structure was measured using echocardiography.
Results: Ascorbate completely prevented the onset of hypertension (105±2 mmHg vs. 95±2 mmHg in Asc treated, P≤0.05) and proteinuria (P≤0.001) in GSNOR–/– mothers. It also significantly improved cardiac output (15±1 ml/min vs. 21±1 ml/min in Asc treated) and stroke volume (31±1 μl vs. 40±2 μl in Asc treated) in GSNOR–/– mothers at late gestation (P≤0.001). In addition, enlarged anterior wall thickness and relative wall thickness indicative of concentric hypertrophy were completely reversed with ascorbate treatment (P≤0.01). Fetal survival was improved (4.5±1 vs. 7.1±1 pups per litter in Asc treated, P≤0.01), whereas fetal growth was not affected with ascorbate treatment.
Conclusion: Together these findings identify the GSNOR–/– as a novel mouse model of preeclampsia, and demonstrate that ascorbate may serve as a therapy supplement to prevent or treat this disorder. These findings have important pathophysiological and therapeutic implications for PIH.
- © 2013 by American Heart Association, Inc.