Prostaglandin E₂ Receptor EP4 Inhibition Contracts Rat Ductus Arteriosus Prostaglandin E<sub>2</sub> Receptor EP4 Inhibition Contracts Rat Ductus Arteriosus

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Author(s)

Abstract

<p><b><i>Background:</i></b>Patent ductus arteriosus (PDA) is common in premature infants. Cyclooxygenase inhibitors such as indomethacin, which inhibit prostaglandin E<sub>2</sub>(PGE<sub>2</sub>) synthesis, are currently the sole treatments for patients with PDA. Their efficacy are, however, frequently limited, and adverse effects are problematic. Because the PGE<sub>2</sub>-specific receptor EP4 selectively expresses in rat ductus arteriosus (DA), it is hypothesized that EP4 inhibition would promote DA closure with fewer side-effects.</p><p><b><i>Methods and Results:</i></b>A new chemical compound EP4 antagonist, RQ-15986 (renamed from CJ-042794), was used. Whether RQ-15986 selectively contracted the DA was examined by measuring the isometric tension of rat DA ex vivo at embryonic day 19 (e19) and e21. RQ-15986 at a dose of 10<sup>−6</sup>mol/L increased the isometric tension of the DA up to 44.8±6.2% and 69.1±12.9% to the maximal KCl-induced tension at e19 and e21 respectively. The effect of RQ-15986 on rat DA in vivo was also tested by using a rapid whole-body freezing method. RQ-15986 inhibited PGE<sub>1</sub>-induced DA dilatation in neonatal rats. Furthermore, RQ-15986 contracted the DA in a dose-dependent manner, and the constriction was greater at e21 than at e19. Moreover, RQ-15986 did not contract the aorta or the marginal artery of the colon.</p><p><b><i>Conclusions:</i></b>EP4 inhibition contracts rat DA with fewer side-effects. EP4 inhibition is a promising alternative strategy to treat patients with PDA.</p>

Journal

  • Circulation Journal

    Circulation Journal 83(1), 209-216, 2018

    The Japanese Circulation Society

Codes

  • NII Article ID (NAID)
    130007550525
  • NII NACSIS-CAT ID (NCID)
    AA11591968
  • Text Lang
    ENG
  • ISSN
    1346-9843
  • NDL Article ID
    029414280
  • NDL Call No.
    Z54-B860
  • Data Source
    NDL  J-STAGE 
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