Corticosterone Synthesis Inhibitor-Induced Decrease in the Age-Dependant Expression of Nitric Oxide Synthase 3 in the Preterm Ductus Arteriosus of Rats

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Previous studies have shown that the dilating effect of nitric oxide (NO) on the fetal ductus arteriosus (DA) is age dependent and more marked in the premature stages in rats, but the factors that mediate this effect are poorly understood. The purpose of this study is to determine the changes in the expression of NO synthase (NOS) mRNA in the fetal DA and to examine the effect of an 11-β-hydroxylase inhibitor of corticosterone synthesis, namely, metyrapone, on NOS expression. NOS 3 mRNA expression was observed in 17.5-day-old rat fetuses; thereafter, its level significantly increased and reached its peak on day 19.5 and then decreased until the end of the gestation period (day 21.5). To inhibit corticosterone synthesis, a constant infusion of metyrapone was administered to rats; this significantly decreased the fetal plasma corticosterone concentration as well as NOS 3 mRNA expression in the DA in a time-dependent manner. These results indicate that NO is generated by NOS 3 in the DA and that the age-dependant expression of NOS 3 in the premature DA is attributable to corticosterone-associated activity.