Endothelin in the perinatal circulation.
During the fetal period, blood is oxygenated through the placenta, and most of the cardiac output bypasses the lung through the ductus arteriosus. At birth, pulmonary vascular resistance falls with the initiation of ventilation. Coincidentally, the ductus arteriosus constricts. Endothelin-1 (ET-1) appears to play an important role during that transition period and postnatally. ET-1 can dramatically increase resistance in the placental microcirculation and may be involved in blood flow redistribution with hypoxia. At birth, the increase in oxygen tension is important in triggering ductus vasoconstriction. It is proposed that oxygen triggers closure of the ductus arteriosus by activating a specific, cytochrome P450-linked reaction, which in turn stimulates the synthesis of ET-1. On the neonatal heart, ET-1 has a positive chronotropic but negative inotropic effect. In the newborn piglet and the fetal lamb, both term and preterm, ET-1 causes a potent, long-lasting pulmonary vasoconstriction. Furthermore, a transient dilator response has been identified, and it is ascribed to nitric oxide formation. ET receptors are abundant in the piglet pulmonary vasculature. They are predominantly of the ETA constrictor subtype, though ETB2 constrictor receptors may also be present in certain species. The dilator response is linked to the ETB1 receptor, and the number of ETB1 receptors is reduced in hypoxia-induced pulmonary hypertension. ET-1 appears to be a causative agent in the pathogenesis of hypoxia- and hyperoxia-induced pulmonary hypertension as demonstrated by reversal of hemodynamic and morphological changes with treatment with an ETA receptor antagonist. Findings are amenable to practical applications in the management of infants with pulmonary hypertension or requiring persistent patency of the ductus arteriosus.
Perreault
Thérèse
T
Newborn Medicine, Department of Pediatrics, The Montreal Children's Hospital, McGill University, 2300 Tupper Street, Montreal, QC H3H 1P3, Canada. therese.perreault@muhc.mcgill.ca
Coceani
Flavio
F
D000818:Animals; D000831:Animals, Newborn; D001775:Blood Circulation / Q000502:physiology*; D004373:Ductus Arteriosus / Q000502:physiology; D016232:Endothelins / Q000502:physiology*; D005260:Female; D005312:Fetal Blood / Q000502:physiology; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology; D007231:Infant, Newborn / Q000502:physiology*; D021041:Placental Circulation / Q000502:physiology; D011247:Pregnancy
D016232:Endothelins