Lipopolysaccharide Delays Closure of the Rat Ductus Arteriosus by Induction of Inducible Nitric Oxide Synthase But Not Prostaglandin E₂ Lipopolysaccharide Delays Closure of the Rat Ductus Arteriosus by Induction of Inducible Nitric Oxide Synthase But Not Prostaglandin E<sub>2</sub>

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Abstract

<b><i>Background:</i></b>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.<b><i>Methods and Results:</i></b>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,<i>N</i>ω-Nitro-L-arginine methyl ester hydrochloride, significantly prevented the delayed closure of the DA after birth in neonates from LPS-injected rats.<b><i>Conclusions:</i></b>The present study demonstrated that LPS-mediated infection delayed closure of the rat DA without apparent histological changes. iNOS, but not prostaglandin E<sub>2</sub>, may play a primary role in delayed functional closure of the DA. (<i>Circ J</i> 2016; <b>80:</b> 703–711)

Journal

  • Circulation Journal

    Circulation Journal 80(3), 703-711, 2016

    The Japanese Circulation Society

Codes

  • NII Article ID (NAID)
    130005128466
  • NII NACSIS-CAT ID (NCID)
    AA11591968
  • Text Lang
    ENG
  • ISSN
    1346-9843
  • NDL Article ID
    027128248
  • NDL Call No.
    Z54-B860
  • Data Source
    NDL  J-STAGE 
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