title: Changes in the nitric oxide-soluble guanylate cyclase system and natriuretic peptide receptor system in placentas of pregnant Dahl salt-sensitive rats.
abstract: OBJECTIVE
  Diminished vasodilator activity during pregnancy, which augments vascular responses to vasoconstrictors, is one reason for the onset of pre-eclampsia and superimposed pre-eclampsia. It is known that Dahl salt-sensitive (Dahl-S) rats develop salt-sensitive hypertension like African-Americans. The present study attempted to assess the changes and the interactions of the NOS-NO-sGC-cGMP and NP-NPR-cGMP systems in the hypertensive placenta using Dahl-S rats as an animal model of superimposed pre-eclampsia.
  
  
  METHODS
  Pregnant Dahl-S rats were fed a high-salt diet to induce the development of hypertension and fetal growth restriction. Using these rats, we investigated the regulation of these two vasodilatation systems, including the kinetics of cyclic guanosine monophosphate (cGMP), soluble guanylate cyclase (sGC), endothelial nitric oxide synthase (NOS), cytokine-inducible NOS, natriuretic peptides (NP) (atrial NP, brain NP and C-type NP), and NP receptors (NPR) (NPR-A, NPR-B, NPR-C).
  
  
  RESULTS
  Dahl-S rats fed a high-salt diet exhibited hypertension, fetal growth restriction and thickening of the walls in decidual vessels. The placental cGMP level in the rats fed the high-salt diet was significantly decreased compared with that in controls. The expression levels of endothelial NOS and cytokine-inducible NOS mRNA increased significantly, while that of sGCα2-sunbnit declined significantly. Messenger RNA levels of NPR-C, a clearance-type receptor of NP, declined significantly, whereas those of NP and their functional receptors NPR-A and NPR-B were unchanged.
  
  
  CONCLUSIONS
  As Dahl-S rats with excess salt-loading during pregnancy exhibited pathological changes similar to those observed in female humans with pre-eclampsia/superimposed pre-eclampsia, this rat could be useful as an animal model of superimposed pre-eclampsia. In the placentas of hypertensive Dahl-S rats, vasodilatation seemed to be disturbed by the deregulation of both the NO-sGC-cGMP and NP-NPR-cGMP systems.
authors.affiliation: Department of Obstetrics and Gynecology, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Sachiyo
authors.initials: S
authors.lastname: Takushima
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Nishi
authors.forename: Akiko
authors.initials: A
authors.lastname: Nonoshita
authors.forename: Hiroharu
authors.initials: H
authors.lastname: Mifune
authors.forename: Rumiko
authors.initials: R
authors.lastname: Hirata
authors.forename: Eiichiro
authors.initials: E
authors.lastname: Tanaka
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Doi
authors.forename: Daizo
authors.initials: D
authors.lastname: Hori
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Kamura
authors.forename: Kimio
authors.initials: K
authors.lastname: Ushijima
mesh_terms: D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism*; D005260:Female; D005317:Fetal Growth Retardation / Q000378:metabolism; D006973:Hypertension / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D020303:Rats, Inbred Dahl; D000071756:Soluble Guanylyl Cyclase / Q000378:metabolism*
chemical_list: D009569:Nitric Oxide; D000071756:Soluble Guanylyl Cyclase; D006152:Cyclic GMP
keywords: Dahl-S rat; NOS-NO-sGC system; NP-NPR system; cyclic guanosine monophosphate; superimposed pre-eclampsia