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Sodium thiosulfate in the pregnant dahl salt-sensitive rat, a model of preeclampsia

Sodium thiosulfate in the pregnant dahl salt-sensitive rat, a model of preeclampsia
Sodium thiosulfate in the pregnant dahl salt-sensitive rat, a model of preeclampsia

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/24h), 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.

Blood pressure, Cardiovascular, Dahl salt-sensitive rats, Fetal growth restriction, Hydrogen sulfide, Preeclampsia, Sodium thiosulfate, Therapeutics
1-14
Terstappen, Fieke
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Clarke, Sinéad M.
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Joles, Jaap A.
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Ross, Courtney A.
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Garrett, Michael R.
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Minnion, Magdalena
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Feelisch, Martin
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Goor, Harry van
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Sasser, Jennifer M.
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Lely, A. Titia
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Terstappen, Fieke
2e0dbdfd-fe0d-4ab7-bf39-8a0196ed1d0c
Clarke, Sinéad M.
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Joles, Jaap A.
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Ross, Courtney A.
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Garrett, Michael R.
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Minnion, Magdalena
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Feelisch, Martin
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Goor, Harry van
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Sasser, Jennifer M.
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Lely, A. Titia
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Terstappen, Fieke, Clarke, Sinéad M., Joles, Jaap A., Ross, Courtney A., Garrett, Michael R., Minnion, Magdalena, Feelisch, Martin, Goor, Harry van, Sasser, Jennifer M. and Lely, A. Titia (2020) Sodium thiosulfate in the pregnant dahl salt-sensitive rat, a model of preeclampsia. Biomolecules, 10 (2), 1-14, [302]. (doi:10.3390/biom10020302).

Record type: Article

Abstract

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/24h), 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.

Text
2020 Terstappen Biomolecules - Version of Record
Available under License Creative Commons Attribution.
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More information

Accepted/In Press date: 12 February 2020
e-pub ahead of print date: 14 February 2020
Published date: February 2020
Keywords: Blood pressure, Cardiovascular, Dahl salt-sensitive rats, Fetal growth restriction, Hydrogen sulfide, Preeclampsia, Sodium thiosulfate, Therapeutics

Identifiers

Local EPrints ID: 439797
URI: http://eprints.soton.ac.uk/id/eprint/439797
PURE UUID: 08f8c755-5790-4a4f-a95c-af3e3cac7d99
ORCID for Martin Feelisch: ORCID iD orcid.org/0000-0003-2320-1158

Catalogue record

Date deposited: 04 May 2020 16:34
Last modified: 26 Nov 2021 02:58

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Contributors

Author: Fieke Terstappen
Author: Sinéad M. Clarke
Author: Jaap A. Joles
Author: Courtney A. Ross
Author: Michael R. Garrett
Author: Magdalena Minnion
Author: Martin Feelisch ORCID iD
Author: Harry van Goor
Author: Jennifer M. Sasser
Author: A. Titia Lely

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