Attenuation of the vasoconstrictor effects of thromboxane and endothelin by nitric oxide in the human fetal-placental circulation.
OBJECTIVE
We hypothesized that the endothelial-derived relaxing factor nitric oxide may contribute to low resting vascular tone and may attenuate vasoconstrictor action in the human fetal-placental circulation.


METHODS
Isolated human placental cotyledons were dually perfused in vitro, and the effects of N-monomethyl-L-arginine and N-nitro-L-arginine (3 x 10(-4) mol/L), which are nonmetabolizable analogs of L-arginine, the substrate for nitric oxide synthase, on resting perfusion pressure and on the fetal-placental circulation preconstricted with U46619 (10(-8) mol/L) or endothelin-1 (10(-8) mol/L) were established. Responses before and after inhibition were compared by paired t test. The effects of glyceryl trinitrate (10(-6) mol/L), acetylcholine (10(-4) mol/L), the calcium ionophore A23187 (10(-6) mol/L), and histamine (10(-8) to 10(-4) mol/L) were also determined in the preconstricted fetal-placental circulation.


RESULTS
Both N-monomethyl-L-arginine and N-nitro-L-arginine (3 x 10(-4) mol/L) increased resting perfusion pressure (p less than 0.06), and N-nitro-L-arginine promptly and significantly increased perfusion pressure in the fetal-placental circulation preconstricted with U46619 (p less than 0.0004) or endothelin-1 (p less than 0.06). Nitric oxide generated by addition of glyceryl trinitrate (10(-6) mol/L) attenuated the vasoconstrictor effects of U46619 (p less than 0.026) or endothelin-1 (p less than 0.01). Neither acetylcholine nor the calcium ionophore A23187 had an effect on the fetal-placental circulation, whereas bradykinin further increased perfusion pressure. Histamine only relaxed the preconstricted preparations at concentrations (10(-6) to 10(-4) mol/L) above those shown to release nitric oxide in other systems.


CONCLUSIONS
The stimulus to nitric oxide generation in the fetal-placental circulation may be hydrodynamic. Nitric oxide appears to contribute to maintenance of basal vascular tone and to attenuate the actions of vasoconstrictors in this circulation.
Myatt
L
L
Perinatal Research Institute, University of Cincinnati College of Medicine, OH 45267-0526.
Brewer
A S
AS
Langdon
G
G
Brockman
D E
DE
D000109:Acetylcholine / Q000494:pharmacology; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D016232:Endothelins / Q000494:pharmacology*; D005260:Female; D005333:Fetus / Q000098:blood supply*; D006801:Humans; D009569:Nitric Oxide / Q000494:pharmacology*; D019335:Nitroarginine; D005996:Nitroglycerin / Q000494:pharmacology; D010920:Placenta / Q000098:blood supply*; D011247:Pregnancy; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*; D019323:omega-N-Methylarginine
D016232:Endothelins; D011450:Prostaglandin Endoperoxides, Synthetic; D019335:Nitroarginine; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D000001:Calcimycin; D001120:Arginine; D005996:Nitroglycerin; D000109:Acetylcholine