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Sodium hydrosulfide prevents hypertension and increases in vascular endothelial growth factor and soluble fms-like tyrosine kinase-1 in hypertensive pregnant rats

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Abstract

Sodium hydrosulfide (NaHS) has presented antihypertensive and antioxidant effects and may reduce circulating soluble fms-like tyrosine kinase-1 (sFlt-1). We examined whether NaHS prevents maternal and fetal detrimental changes in a model of hypertension in pregnancy induced by N(G)-nitro-L-arginine methyl ester (L-NAME). Forty pregnant rats were divided into four groups (n = 10 per group): Norm-Preg, Preg + NaHS, HTN-Preg, or HTN-Preg + NaHS. Systolic blood pressure (SBP), number of viable fetuses, litter size, pups, and placentae weights were recorded. Circulating plasma sFlt-1, vascular endothelial growth factor (VEGF), myeloperoxidase (MPO), trolox equivalent antioxidant capacity (TEAC) levels, and biochemical determinants of nitric oxide (NO) formation were assessed. SBP values were elevated in the HTN-Preg group on gestational days 16, 18, and 20. However, HTN-Preg + NaHS group presented lower SBP values on days 18 and 20. Lower number of viable fetuses and litter size were found only in HTN-Preg group compared to other. Reductions in placental weight were found in HTN-Preg and HTN-Preg + NaHS groups. Increases in fetal weight were found only in Preg + NaHS group. Increases in circulating sFlt-1 and VEGF levels were observed only in HTN-Preg group compared to other. Higher MPO and lower TEAC plasma levels were found in HTN-Preg + NaHS and HTN-Preg groups. NO was diminished in HTN-Preg animals, and NaHS treatment increased NO levels only in hypertensive pregnant animals. Treatment with NaHS prevents hypertension in pregnancy and concomitantly reduces circulating plasma sFlt-1 and VEGF levels; this correlates with improved litter size with more viable fetuses and increase in NO levels. However, these beneficial effects presented no relation with oxidative stress.

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Acknowledgments

This study was supported by funding from the Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP, Brazil). The following are gratefully acknowledged: Valeria Cristina Sandrim and Helio Kushima for their co-operation and advice with technician issues.

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Authors and Affiliations

  1. Department of Pharmacology, Biosciences Institute of Botucatu, Sao Paulo State University (UNESP), Distrito de Rubiao Junior S/N, 18.618-970, Botucatu, Sao Paulo, Brazil

    Jose Sergio Possomato-Vieira, Victor Hugo Gonçalves-Rizzi, Tamiris Uracs Sales Graça, Regina Aparecida Nascimento & Carlos A. Dias-Junior

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  1. Jose Sergio Possomato-Vieira
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  2. Victor Hugo Gonçalves-Rizzi
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  3. Tamiris Uracs Sales Graça
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  4. Regina Aparecida Nascimento
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  5. Carlos A. Dias-Junior
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Correspondence to Carlos A. Dias-Junior.

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Possomato-Vieira, J.S., Gonçalves-Rizzi, V.H., Graça, T.U.S. et al. Sodium hydrosulfide prevents hypertension and increases in vascular endothelial growth factor and soluble fms-like tyrosine kinase-1 in hypertensive pregnant rats. Naunyn-Schmiedeberg's Arch Pharmacol 389, 1325–1332 (2016). https://doi.org/10.1007/s00210-016-1296-5

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