Background and Aims Sulfonylureas inhibit the ATP-sensitive potassium (KATP) channel, are insulinogenic, and close the fetal ductus arteriosus. Diazoxide, a KATP channel opener, is used for neonatal hyperinsulinemic hypoglycemia, and has been associated with the reopening of the ductus arteriosus. The aim of this study is to clarify ductus-opening effect of diazoxide.
Methods Neonatal rats were delivered by caesarian section near-term and incubated at 34°C. Diazoxide and pinacidil, another KATP channel opener, were injected intraperitoneally immediately, or at one hour, or at four hours postnatally, and the ductus was studied 0.5, and 1 hour later, with a rapid whole-body freezing method.
Results Diazoxide and pinacidil both induced hyperglycemia. Diazoxide and pinacidil delayed neonatal ductus closure following injection immediately after birth. At 2 hours, the control ductus was closed, whereas the ductus treated with 100 mg/kg of diazoxide at birth was widely patent with a diameter 40% of the fetal ductus. Ductus diameter at 60 minutes postnatally dilated from 10% to 40% with diazoxide. Diazoxide given to the closed ductus at 4 hours after birth did not open reopen it. The ductus was more sensitive to pinacidil than to diazoxide.
Conclusions Diazoxide and pinacidil open the closing ductus arteriosus of the neonatal rat. This study demonstrates that opening of KATP channels results in opening of the ductus arteriosus, indicating that the KATP channel is physiologically and pharmacologically important in ductus opening. The ductus should be checked in the neonate before and after treatment with diazoxide.