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Dilatation of the ductus arteriosus by diazoxide in fetal and neonatal rats
Author(s) -
Toyoshima Katsuaki,
Momma Kazuo,
Ishii Tetsuko,
Nakanishi Toshio
Publication year - 2017
Publication title -
pediatrics international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.49
H-Index - 63
eISSN - 1442-200X
pISSN - 1328-8067
DOI - 10.1111/ped.13424
Subject(s) - medicine , ductus arteriosus , diazoxide , fetus , cardiology , fetal circulation , anesthesia , pregnancy , placenta , insulin , biology , genetics
Background Diazoxide, an ATP ‐sensitive potassium channel opener, is the main therapeutic agent for treating hyperinsulinemic hypoglycemia. The aim of this study was to determine the in vivo ductus arteriosus ( DA )‐dilating effects of diazoxide in fetal and neonatal rats. Methods Near‐term rat pups delivered via cesarean section were housed at 33°C. After rapid whole‐body freezing, the ductus arteriosus ( DA ) diameter was measured using a microscope and a micrometer. Full‐term pregnant rats (gestational day 21) were injected i.p. with diazoxide (10 and 100 mg/kg) 4 h before delivery, and the neonatal DA diameter was measured at 0, 30, or 60 min after birth. The newborn rats were also injected i.p. with diazoxide (10 and 100 mg/kg) at birth or 60 min after birth. DA was measured at 0, 30, or 60 min after injection. In the fetal investigation, the effect of diazoxide was studied via simultaneous application of indomethacin (10 mg/kg) and L‐nitroarginine methyl ester (L‐ NAME ) on gestational days 21 and 19. Results The control rats had rapid postnatal DA constriction (diameter, 0.80 and 0.08 mm at 0 and 60 min after birth, respectively). Diazoxide had a dose‐dependent inhibitory effect on postnatal DA constriction. Prenatal diazoxide (10 mg/kg) inhibited postnatal DA closure (0.20 mm at 60 min after birth). The diazoxide injection (10 mg) at birth inhibited postnatal DA closure (0.14 mm at 60 min after birth). Diazoxide injection in 60‐min‐old rats dilated the constricted DA at 60 min (0.10 mm vs. 0.02 mm in the controls). In the fetal investigation, diazoxide inhibited the fetal DA constrictive effect of indomethacin and L‐ NAME . Conclusion Diazoxide attenuates postnatal DA constriction and dilates a closing DA in fetal and neonatal rats.