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

Naunyn Schmiedebergs Arch Pharmacol. 2016 Dec;389(12):1325-1332. doi: 10.1007/s00210-016-1296-5. Epub 2016 Sep 12.

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.

Keywords: Hydrogen sulfide donor; N(G)-nitro-L-arginine methyl ester; Preeclampsia; Rats.

MeSH terms

  • Animals
  • Antihypertensive Agents / pharmacology*
  • Biomarkers / blood
  • Blood Pressure / drug effects*
  • Disease Models, Animal
  • Down-Regulation
  • Female
  • Fetal Viability / drug effects
  • Fetal Weight / drug effects
  • Gestational Age
  • Hypertension, Pregnancy-Induced / chemically induced
  • Hypertension, Pregnancy-Induced / enzymology
  • Hypertension, Pregnancy-Induced / physiopathology
  • Hypertension, Pregnancy-Induced / prevention & control*
  • Litter Size / drug effects
  • NG-Nitroarginine Methyl Ester
  • Nitric Oxide / metabolism
  • Oxidative Stress
  • Peroxidase / blood
  • Placentation / drug effects
  • Pregnancy
  • Rats, Wistar
  • Sulfides / pharmacology*
  • Vascular Endothelial Growth Factor A / blood*
  • Vascular Endothelial Growth Factor Receptor-1 / blood*

Substances

  • Antihypertensive Agents
  • Biomarkers
  • Sulfides
  • Vascular Endothelial Growth Factor A
  • vascular endothelial growth factor A, rat
  • Nitric Oxide
  • Peroxidase
  • Flt1 protein, rat
  • Vascular Endothelial Growth Factor Receptor-1
  • sodium bisulfide
  • NG-Nitroarginine Methyl Ester