Gestational changes in endothelium-dependent vasorelaxation in human umbilical artery.
OBJECTIVE
We intended to clarify whether (1) the amount of endothelium-derived vasorelaxing factor or nitric oxide released by histamine is sufficient to cause relaxation in human umbilical artery at different stages of gestation and (2) the functional role of endothelium-derived relaxing factor changes with the progress of gestation.


METHODS
By means of a bioassay cascade technique with very thin muscle strips, which allows rapid diffusional access of applied drugs (of the order of a few seconds), contractile properties were examined.


RESULTS
At 18 to 22 weeks of gestation histamine produced only a minor contraction, but as gestation progressed the contractile responses increased. L-NG-nitro-arginine greatly enhanced the histamine-induced contractions. Histamine produced a concentration-dependent relaxation during the maintained contraction induced by 39 mmol/L K+ in tissues from 18 to 22 weeks or 30 to 32 weeks but not 38 to 41 weeks of gestation. Thus the concentration-relaxation relationship for histamine showed decreased sensitivity during gestation. The histamine-induced relaxation was enhanced by superoxide dismutase and completely blocked by L-NG-nitro-arginine or mepyramine (H1 antagonist). The concentration-relaxation relationship for the action of glycerol trinitrate relaxation decreased as gestation progressed. In a bioassay cascade an endothelium-intact umbilical artery from 18 to 22 or 38 to 41 weeks of gestation was used as a "donor" and L-NG-nitro-arginine-treated umbilical artery from 18 to 22 and 38 to 41 weeks as a "detector." In the presence of histamine the perfusate that had passed through a donor from 18 to 22 weeks (but not 38 to 41 weeks) attenuated the high K(+)-induced contraction in the detector only from 18 to 22 weeks.


CONCLUSIONS
These results suggest that the amount of endothelium-derived relaxing factor and the sensitivity of smooth muscle to endothelium-derived relaxing factor decreased with the progress of gestation.
Izumi
H
H
Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston 77551.
Garfield
R E
RE
Makino
Y
Y
Shirakawa
K
K
Itoh
T
T
D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001681:Biological Assay; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D006632:Histamine / Q000494:pharmacology / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology*; D019335:Nitroarginine; D005996:Nitroglycerin / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011247:Pregnancy / Q000502:physiology*; D011262:Pregnancy Trimester, Second; D011263:Pregnancy Trimester, Third; D011738:Pyrilamine / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000494:pharmacology; D014469:Umbilical Arteries / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D019335:Nitroarginine; D009569:Nitric Oxide; D006632:Histamine; D001120:Arginine; D013482:Superoxide Dismutase; D005996:Nitroglycerin; D011738:Pyrilamine; D011188:Potassium