Toyoshima Katsuaki, Momma Kazuo, Ishii Tetsuko, Nakanishi Toshio
Division of Pediatric Cardiology, Tokyo Women's Medical University, Tokyo, Japan.
Division of Neonatology, Kanagawa Children's Medical Center, Yokohama, Japan.
Pediatr Int. 2017 Dec;59(12):1246-1251. doi: 10.1111/ped.13424.
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.
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.
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.
Diazoxide attenuates postnatal DA constriction and dilates a closing DA in fetal and neonatal rats.
二氮嗪是一种ATP敏感性钾通道开放剂，是治疗高胰岛素血症性低血糖的主要治疗药物。本研究的目的是确定二氮嗪对胎鼠和新生大鼠动脉导管（DA）的体内扩张作用。
通过剖宫产分娩的近足月幼鼠饲养在33°C环境中。快速全身冷冻后，使用显微镜和测微计测量动脉导管（DA）直径。足月妊娠大鼠（妊娠第21天）在分娩前4小时腹腔注射二氮嗪（10和100mg/kg），并在出生后0、30或60分钟测量新生大鼠的DA直径。新生大鼠在出生时或出生后60分钟也腹腔注射二氮嗪（10和100mg/kg）。在注射后0、30或60分钟测量DA。在胎儿研究中，在妊娠第21天和第19天同时应用吲哚美辛（10mg/kg）和L-精氨酸甲酯（L-NAME）研究二氮嗪的作用。
对照大鼠出生后DA迅速收缩（出生后0和60分钟时直径分别为0.80和0.08mm）。二氮嗪对出生后DA收缩有剂量依赖性抑制作用。产前二氮嗪（10mg/kg）抑制出生后DA关闭（出生后60分钟时为0.20mm）。出生时注射二氮嗪（10mg）抑制出生后DA关闭（出生后60分钟时为0.14mm）。对60日龄大鼠注射二氮嗪可使60分钟时收缩的DA扩张（0.10mm vs. 对照组的0.02mm）。在胎儿研究中，二氮嗪抑制吲哚美辛和L-NAME对胎儿DA的收缩作用。
二氮嗪可减轻出生后DA收缩，并使胎鼠和新生大鼠正在关闭的DA扩张。
