L-arginine prevents hypoxia-induced vasoconstriction in dual-perfused human placental cotyledons.
Palabras clave
Abstracto
BACKGROUND
Chronic hypoxia in the uteroplacental unit is associated with increased resistance to blood flow in the fetal-placental circulation. These changes can lead to adverse cardiovascular events in adulthood. This study investigates whether L-arginine (substrate for nitric oxide synthase (NOS) or endothelin-A receptor antagonist BQ123 administration reverses hypoxia-induced changes in perfusion pressure in the fetal compartment in dual-perfused placental cotyledons.
METHODS
Human placental cotyledons (n = 15) from term deliveries (n = 15) were perfused with Krebs solution from maternal and fetal sides. Normal and reduced oxygen tension conditions were sequentially created in the perfused maternal compartment. Fetal perfusion pressure was continuously monitored. 1 mM L-arginine, D-arginine (an enantiomer of L-arginine and not a substrate for NOS), and BQ123 or normal saline were administered to the fetal compartment; L-arginine was also administered to the maternal compartment prior to maternal side hypoxia. Changes in perfusion pressure were compared between groups.
RESULTS
Maternal hypoxia increased (19 ± 6%) perfusion pressure and this was blunted by L-arginine injection (3 ± 5%; p = 0.006) into the fetal compartment. L-arginine in the maternal compartment had no significant effect (22 ± 4% with L-arginine vs.14 ± 3% at control) on perfusion pressure. Similarly, D-arginine (23 ± 11% vs.19 ± 8% at control) or BQ123 (12 ± 3% vs.13 ± 3% at control) in the fetal compartment did not blunt the hypoxia-induced increase in perfusion pressure.
CONCLUSIONS
Fetal vasoconstriction induced by maternal hypoxia is blunted by NO synthase substrate L-arginine, but not by D-arginine, in the fetal compartment, suggesting the involvement of NO synthesis in regulating the hypoxia-induced fetal vasoconstriction. Endothelin A receptor-related mechanisms does not appear to play a role in the maternal hypoxia-induced fetal vasoconstriction.
