L-arginine prevents hypoxia-induced vasoconstriction in dual-perfused human placental cotyledons.
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.
Department of Obstetrics & Gynecology, Baylor College of Medicine, Houston, TX 77030, USA.
Andrey
A
Bednov
Department of Obstetrics & Gynecology, Baylor College of Medicine, Houston, TX 77030, USA.
Jimmy
J
Espinoza
Department of Obstetrics & Gynecology, Baylor College of Medicine, Houston, TX 77030, USA.
Ancizar
A
Betancourt
Department of Obstetrics & Gynecology, Baylor College of Medicine, Houston, TX 77030, USA; 21 Back Bay Cir., Galveston, TX 77551, USA.
Yuri
Y
Vedernikov
Department of Obstetrics & Gynecology, Baylor College of Medicine, Houston, TX 77030, USA.
Michael
M
Belfort
Department of Obstetrics & Gynecology, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: cyallamp@bcm.edu.
Chandrasekhar
C
Yallampalli
D001120:Arginine / Q000494:pharmacology* / Q000627:therapeutic use; D065128:Endothelin Receptor Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000188:drug therapy*; D066298:In Vitro Techniques; D010456:Peptides, Cyclic / Q000494:pharmacology* / Q000627:therapeutic use; D010920:Placenta / Q000098:blood supply / Q000187:drug effects*; D011247:Pregnancy; D014661:Vasoconstriction / Q000187:drug effects*
D065128:Endothelin Receptor Antagonists; D010456:Peptides, Cyclic; D001120:Arginine; C072247:cyclo(Trp-Asp-Pro-Val-Leu)
Cardiovascular; Fetus; Hypoxia; Remodeling; l-arginine