title: Lipopolysaccharide Delays Closure of the Rat Ductus Arteriosus by Induction of Inducible Nitric Oxide Synthase But Not Prostaglandin E2.
abstract: BACKGROUND
  The incidence of patent ductus arteriosus is known to be higher in premature neonates with infection than in those without infection. However, the detailed mechanism has not been investigated.
  
  
  RESULTS
  Lipopolysaccharide (LPS; 100 μg/kg) was injected into timed-pregnant Wistar rats on day 18 and 19 of pregnancy. The fetuses were delivered by cesarean section on gestational day 21. Using a rapid whole-body freezing method, it was found that closure of the ductus arteriosus (DA) was significantly delayed in neonates from LPS-injected rats after birth. Histological analysis demonstrated that there was no difference in vascular remodeling of the DA. Quantitative reverse transcriptase-polymerase chain reaction analysis showed that the tumor necrosis factor α and inducible nitric oxide synthase (iNOS) mRNA expression level was significantly increased, but there was no difference in cyclooxygenase 2 and prostaglandin receptor, EP4, mRNA expression in the DA from LPS-injected rats. Moreover, the NOS inhibitor,Nω-Nitro-L-arginine methyl ester hydrochloride, significantly prevented the delayed closure of the DA after birth in neonates from LPS-injected rats.
  
  
  CONCLUSIONS
  The present study demonstrated that LPS-mediated infection delayed closure of the rat DA without apparent histological changes. iNOS, but not prostaglandin E2, may play a primary role in delayed functional closure of the DA. (Circ J 2016; 80: 703-711).
authors.affiliation: Department of Cell Physiology, The Jikei University School of Medicine.
authors.forename: Ichige
authors.initials: I
authors.lastname: Kajimura
authors.forename: Toru
authors.initials: T
authors.lastname: Akaike
authors.forename: Susumu
authors.initials: S
authors.lastname: Minamisawa
mesh_terms: D000818:Animals; D015232:Dinoprostone / Q000378:metabolism; D004373:Ductus Arteriosus / Q000196:embryology*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000633:toxicity*; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis*; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar
chemical_list: D008070:Lipopolysaccharides; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D015232:Dinoprostone