title: Sodium nitrite attenuates hypertension-in-pregnancy and blunts increases in soluble fms-like tyrosine kinase-1 and in vascular endothelial growth factor.
abstract: Preeclampsia is a pregnancy-associated disorder characterized by hypertension with uncertain pathogenesis. Increases in antiangiogenic soluble fms-like tyrosine kinase-1 (sFlt-1) and reductions in nitric oxide (NO) bioavailability have been observed in preeclamptic women. However, the specific mechanisms linking these detrimental changes to the hypertension-in-pregnancy are not clearly understood. In this regard, while recent findings have suggested that nitrite-derived NO formation exerts antihypertensive and antioxidant effects, no previous study has examined these responses to orally administered nitrite in hypertension-in-pregnancy. We then hypothesized restoring NO bioavailability with sodium nitrite in pregnant rats upon NO synthesis inhibition with N(omega)-nitro-l-arginine methyl ester (L-NAME) attenuates hypertension and high circulating levels of sFlt-1. Number and weight of pups and placentae were recorded to assess maternal-fetal interface. Plasma sFlt-1, vascular endothelial growth factor (VEGF) and biochemical determinants of NO formation and of antioxidant function were measured. We found that sodium nitrite blunts the hypertension-in-pregnancy and restores the NO bioavailability, and concomitantly prevents the L-NAME-induced high circulating sFlt-1 and VEGF levels. Also, our results suggest that nitrite-derived NO protected against reductions in litter size and placental weight caused by L-NAME, improving number of viable and resorbed fetuses and antioxidant function. Therefore, the present findings are consistent with the hypothesis that nitrite-derived NO may possibly be the driving force behind the maternal and fetal beneficial effects observed with sodium nitrite during hypertension-in-pregnancy. Certainly further investigations are required in preeclampsia, since counteracting the damages to the mother and fetal sides resulting from hypertension and elevated sFlt-1 levels may provide a great benefit in this gestational hypertensive disease.
authors.affiliation: Department of Pharmacology, Biosciences Institute of Botucatu, Sao Paulo State University (UNESP), Botucatu, Sao Paulo, Brazil.
authors.forename: Victor Hugo
authors.initials: VH
authors.lastname: Gonçalves-Rizzi
authors.affiliation: Department of Pharmacology, Biosciences Institute of Botucatu, Sao Paulo State University (UNESP), Botucatu, Sao Paulo, Brazil.
authors.forename: Jose Sergio
authors.initials: JS
authors.lastname: Possomato-Vieira
authors.affiliation: Department of Pharmacology, Biosciences Institute of Botucatu, Sao Paulo State University (UNESP), Botucatu, Sao Paulo, Brazil.
authors.forename: Tamiris Uracs
authors.initials: TU
authors.lastname: Sales Graça
authors.affiliation: Department of Pharmacology, Biosciences Institute of Botucatu, Sao Paulo State University (UNESP), Botucatu, Sao Paulo, Brazil.
authors.forename: Regina Aparecida
authors.initials: RA
authors.lastname: Nascimento
authors.affiliation: Department of Pharmacology, Biosciences Institute of Botucatu, Sao Paulo State University (UNESP), Botucatu, Sao Paulo, Brazil. Electronic address: carlosjunior@ibb.unesp.br.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Dias-Junior
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D046110:Hypertension, Pregnancy-Induced / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D008098:Litter Size / Q000187:drug effects; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000097:blood; D009573:Nitrites / Q000097:blood; D009929:Organ Size; D010920:Placenta / Q000187:drug effects / Q000503:physiopathology; D011247:Pregnancy; D017208:Rats, Wistar; D012977:Sodium Nitrite / Q000008:administration & dosage / Q000627:therapeutic use*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D009566:Nitrates; D009573:Nitrites; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D009569:Nitric Oxide; C501164:Flt1 protein, rat; D040281:Vascular Endothelial Growth Factor Receptor-1; D012977:Sodium Nitrite; D019331:NG-Nitroarginine Methyl Ester
keywords: Hypertension-in-pregnancy; N(G)-nitro-l-arginine methyl ester; Rats; Sodium nitrite