title: Inhibition of nitric oxide synthase lowers fatty acid oxidation in preeclampsia-like mice at early gestational stage.
abstract: BACKGROUND
  Preeclampsia is one of hypertensive disorders in pregnancy. It is associated with abnormal lipid metabolism, including fatty acid oxidation metabolism. Long chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) plays an indispensable role in the oxidation of fatty acids. It has been reported that nitric oxide (NO) is one of the regulatory factors of the fatty acid oxidation pathway. The aim of this research was to investigate whether the nitric oxide synthase (NOS) inhibitor L-NAME may cause down-regulation of LCHAD in the pathogenesis of preeclampsia.
  
  
  METHODS
  Pregnant wild-type (WT) mice were treated with L-NAME or normal saline (NS) during gestation days 7 - 18 (early group), days 11 - 18 (mid group) and days 16 - 18 (late group), and apoE-/- mice served as a control. Systolic blood pressure (SBP), urine protein, feto-placental outcome, plasma lipid levels and NO concentrations were measured, and the expression of mRNA and protein for LCHAD in placental tissue were determined by real-time polymerase chain reaction (RT-PCR) and Western blotting, respectively.
  
  
  RESULTS
  In WT and apoE-/- mice, SBP and urinary protein increased following L-NAME injection. Fetal and placental weights and NO concentrations were reduced and total cholesterol, triglycerides and free fatty acid levels were increased in early and mid L-NAME groups in WT and apoE-/- mice, compared with the NS group. There was no significant difference between the late L-NAME group and NS group. RT-PCR and Western blotting analysis showed that the mRNA and protein levels of LCHAD expression were significantly down-regulated in the early and mid L-NAME groups but not in the late L-NAME group in the WT and apoE-/- mice compared with the corresponding NS groups.
  
  
  CONCLUSIONS
  Inhibition of NO in early and mid gestation in mice may cause hyperlipidemia and suppression of fatty acid oxidation, whereas preeclampsia-like conditions in late gestation may be a maternal vascular response to inhibition of NO.
authors: Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China.
authors: Rui-Qiong
authors: RQ
authors: Ma
authors: Min-Na
authors: MN
authors: Sun
authors: Zi
authors: Z
authors: Yang
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D010084:Oxidation-Reduction; D011225:Pre-Eclampsia / Q000139:chemically induced / Q000209:etiology*; D011247:Pregnancy
chemical_list: D004791:Enzyme Inhibitors; D005227:Fatty Acids; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester