During fetal life, the ductus arteriosus diverts blood away from
the fluid-filled lungs toward the descending aorta and placenta.
In full-term infants, obliteration of the ductus arteriosus takes
place after birth through a process of vasoconstriction and anatomic
remodeling. Premature infants frequently fail to close their ductus
arteriosus. The clinical consequences of a patent ductus arteriosus
(PDA) are related to the degree of left-to-right shunt through the
PDA with its associated change in blood flow to the lungs, kidneys,
In the full-term infant, closure of the ductus arteriosus occurs
in 2 phases: (1) functional closure of the lumen
within the first hours after birth by smooth muscle constriction
and (2) anatomic occlusion of the lumen over the
next several days due to extensive neointimal thickening and loss
of smooth muscle cells from the inner muscle media.
Balance between Vasoconstriction
Although the fetal ductus arteriosus was originally thought to
be a relatively passive structure that constricted after birth,
it is now clear that, even in utero, the ductus has an active tone.
Ductus arteriosus patency, therefore, is determined by the balance
between dilating and constricting forces. The factors known to play
a prominent role in ductus arteriosus regulation involve those that
promote constriction (oxygen, endothelin, calcium channels, catecholamines,
and Rho kinase) and those that oppose it (intraluminal pressure,
prostaglandins, nitric oxide, carbon monoxide, potassium channels,
and cyclic adenosine monophosphate and cyclic guanosine monophosphate).
The relative importance of each of these factors depends on the
intrauterine and extrauterine environment, the degree of ductus maturation,
and the genetic background and species being studied.
The fetal ductus normally has a high level of intrinsic tone.1 The
intrinsic tone is due to mechanisms that both depend on and are
independent of extracellular calcium.1 The contractile
proteins (smooth muscle myosin, calponin, and caldesmon) are more
differentiated in the ductus than they are in adjacent fetal arteries.2-4 In
addition, the fetal ductus arteriosus is more sensitive to the contractile
effects of calcium than are the aorta and the pulmonary artery.
Other potential factors contributing to ductus tone in utero include
an increased Rho kinase activity in the ductus,6 endothelin-1,7 and
catecholamines that circulate in high concentrations following birth.8-10
The factors that oppose ductus arteriosus constriction in utero
are better understood. The elevated vascular pressure within the
ductus lumen (due to the constricted pulmonary vascular bed) plays
an important role in opposing ductus constriction.11 The
fetal ductus also produces several vasodilators that maintain ductus
patency. Vasodilator prostaglandins appear to be the dominant vasodilators that
oppose ductus constriction in the later part of gestation.12 Inhibitors
of prostaglandin synthesis constrict the fetal ductus both in vitro and
Prostaglandin E2 is the most potent prostaglandin produced
by the ductus and placenta,13,14 and appears to ...