Aberrant production of hydrogen sulfide (H2S) has been linked to preeclampsia. We hypothesized that sodium thiosulfate (STS), a H2S donor, reduces hypertension and proteinuria, and diminishes fetal growth restriction in the Dahl salt-sensitive (S) rat, a spontaneous model of superimposed preeclampsia. In addition to a control group (n = 13), two groups received STS via drinking water at a dose of 2 g (n = 9) or 3 g per kg body weight per day (n = 8) from gestational day (GD) 10 to 20. Uterine artery resistance index was measured (GD18), urinary protein excretion rate was determined (GD19), and blood pressure and fetal outcomes were evaluated (GD20). At 2 g, STS had no effect on preeclamptic symptoms or fetal outcome. At 3 g, STS reduced maternal hypertension (121.8 ± 3.0 vs. 136.3 ± 2.9), but increased proteinuria (89 ± 15 vs. 56 ± 5 mg/24 h), and relative kidney weight (0.86 ± 0.04 vs. 0.73 ± 0.02%). Fetal/placental weight ratio was reduced (3.83 ± 0.07 vs. 4.31 ± 0.08) without affecting litter size. No differences in uterine artery flow or renal histological damage were noted across treatment groups. While these data suggest a promising antihypertensive effect that could imply prolongation of preeclamptic pregnancies, the unfavorable effects on proteinuria, kidney weight, and fetal/placental weight ratio implies that clinical implementation of STS is contra-indicated until safety for mother and child can be verified.
Preeclampsia, a hypertensive disorder of pregnancy, is detrimental to both mother and fetus; however, there is currently no effective treatment for preeclampsia. The anti‐angiogenic protein sFlt‐1 has been implicated in the pathogenesis of preeclampsia through both clinical and experimental studies, leading us and others to propose that antagonism of sFlt‐1 via administration of vascular endothelial growth factor (VEGF) will reduce the maternal symptoms of hypertension and proteinuria in preeclamptic pregnancy. In this study, we tested the hypothesis that VEGF fused to the synthetic carrier elastin like polypeptide (ELP) will improve the maternal syndrome in the Dahl S rat model of superimposed preeclampsia. Female Dahl S rats (16–18 weeks of age) were placed in metabolic cages for 24‐hour urine collection, mated with Dahl S male rats, and randomly divided into control and ELP‐VEGF treated groups. ELP‐VEGF was administered via osmotic pump (5 mg/kg/day, Alzet 2ML1) beginning on day 10 of pregnancy, and pumps were replaced on day 17 of pregnancy. Urine was collected again on day 19, and blood and tissues were harvested on day 20. Urinary protein excretion (Bradford assay) did not differ between groups at baseline (87±11 vs 99±21 mg/d), but was significantly lower during late pregnancy in the ELP‐VEGF treated rats (* p=0.004, table). A subset of ELP‐VEGF‐treated rats (n=4) was implanted with telemetry transmitters (DSI) before mating. While previous studies have shown that blood pressure increases during pregnancy in the Dahl S rat, ELP‐VEGF treatment resulted in a fall in mean arterial pressure of 27±5 mmHg from day 9 to day 18 of pregnancy. No significant differences in fetal growth or litter size were observed following treatment. These data suggest that ELP‐VEGF treatment improves the maternal syndrome of preeclampsia without impairing fetal outcomes.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Hypertension is a major health care disorder affecting up to one in three adults in the United States and is a major risk factor for multiple diseases including coronary artery disease, stroke, congestive heart failure, and end-organ damage. Previous studies have proposed that hypertension is partly driven by an increase in autoantibodies and immunological changes that lead to increased blood pressure. In this study, we tested the hypothesis that treatment with Bortezomib (BTZ), a proteasome inhibitor approved for the treatment of multiple myeloma and mantle cell lymphoma, would attenuate the increase in blood pressure and accompanying rise in urinary protein excretion in the Dahl S and Angiotensin II (Ang II) infused Sprague Dawley (SD) rat models of hypertension. Telemetry implants were placed in the femoral artery for continuous monitoring of mean arterial pressure (MAP) in male Dahl S and SD rats (~14 weeks old, maintained on a normal salt diet), and rats were allowed to recover for one week before baseline urine and MAP were collected. Then, Ang II (400ng/kg/hr) osmotic mini-pumps were implanted in SD rats, and BTZ treatment (0.2 mg/kg twice weekly, s.c.) was started in both Dahl S and SD rats. Ang II mini-pumps were replaced at 2 weeks, and urine was collected at weeks 2 and 4. MAP was reduced by BTZ in Dahl S rats, but no effect was observed in control or Ang II treated SD rats (Table 1). BTZ had no effect on urinary protein excretion (Bradford assay) in any group. These data show that administration of Bortezomib attenuates hypertension in Dahl S but not Ang II hypertension.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.