The effect of doxapram on fetal rabbit ductus arteriosus

Doxapram (DOP) is a respiratory stimulant that has been used as a second-line drug for the treatment of idiopathic apnea of prematurity unresponsive to methylxanthine therapy. The direct action of DOP on blood vessels is poorly understood. Furthermore, no reports have examined the effect of this therapy on the ductus arteriosus, a structure that frequently complicates low birth weight infants. To clarify the effects of the drug on the arterial vessel contractile system, we investigated the direct effect of DOP on the contractile profiles of the ductus arteriosus from fetal rabbit. The concentrations of doxapram used in clinical applications did not demonstrate any depressive or augmentative effects on the contractions of tissue preparations under hypoxic (PO₂ 30 mmHg) conditions. No relaxation of ductal tension was seen following DOP treatment after contraction by hyperoxia (PO ₂ 100-120 mmHg), indomethcin (1 μM), or high-K⁺ (120 mM). Our results indicate that therapeutic concentrations of DOP do not demonstrate any direct effects on the contractile mechanism of the ductus arteriosus in fetal rabbits.