Sodium hydrosulfide prevents hypertension and increases in vascular endothelial growth factor and soluble fms-like tyrosine kinase-1 in hypertensive pregnant rats.
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.
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
JS
Possomato-Vieira
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.
Victor Hugo
VH
Gonçalves-Rizzi
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.
Tamiris Uracs Sales
TU
Graça
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.
Regina Aparecida
RA
Nascimento
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. carlosjunior@ibb.unesp.br.
Carlos A
CA
Dias-Junior
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects*; D004195:Disease Models, Animal; D015536:Down-Regulation; D005260:Female; D005328:Fetal Viability / Q000187:drug effects; D020567:Fetal Weight / Q000187:drug effects; D005865:Gestational Age; D046110:Hypertension, Pregnancy-Induced / Q000139:chemically induced / Q000201:enzymology / Q000503:physiopathology / Q000517:prevention & control*; D008098:Litter Size / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress; D009195:Peroxidase / Q000097:blood; D010929:Placentation / Q000187:drug effects; D011247:Pregnancy; D017208:Rats, Wistar; D013440:Sulfides / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood*
D000959:Antihypertensive Agents; D015415:Biomarkers; D013440:Sulfides; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D009569:Nitric Oxide; D009195:Peroxidase; C501164:Flt1 protein, rat; D040281:Vascular Endothelial Growth Factor Receptor-1; C025451:sodium bisulfide; D019331:NG-Nitroarginine Methyl Ester
Hydrogen sulfide donor; N(G)-nitro-L-arginine methyl ester; Preeclampsia; Rats