Lamb ductus venosus: evidence of a cytochrome P-450 mechanism in its contractile tension.
We have recently shown that a cytochrome P-450-based mechanism is important for the generation of contractile tension by the ductus arteriosus and have now examined whether the same mechanism operates in the ductus venosus. Carbon monoxide (CO/O2 ratio, 0.27) and cytochrome P-450 inhibitors [metyrapone; 4-phenylimidazole; 14-isocyano, 15-(methoxymethyleneoxy)-5Z,8Z,11Z- eicosatrienoic acid; alpha-naphthoflavone] were tested in vitro on the ductus venosus sphincter from mature fetal lambs. Each preparation was precontracted with indomethacin (2.8 x 10(-6) M). Carbon monoxide completely relaxed the ductus, and its action was reversed by illumination with monochromatic light. Peak photocontraction occurred at 450 nm. With the exception of alpha-naphthoflavone, all cytochrome P-450 inhibitors were also relaxant agents. Alpha-naphthoflavone (the sole type I inhibitor tested) produced instead a modest contraction that was often transient. Relaxation brought about by both carbon monoxide and drugs was fully reversed by the thromboxane A2 analog 9,11-epithio-11,12-methano-thromboxane A2 and by excess potassium (55 mM). Carbon monoxide was equally effective in the intact ductus and the ductus denuded of endothelium, whereas cytochrome P-450 inhibitors were marginally less effective in the latter preparation. These findings indicate that the ductus venosus sphincter, like the ductus arteriosus, relies on an intramural cytochrome P-450 mechanism to develop its contractile tone. The actual constrictor remains to be characterized in both vessels.
Adeagbo
A S
AS
Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada.
Breen
C A
CA
Cutz
E
E
Lees
J G
JG
Olley
P M
PM
Coceani
F
F
D000818:Animals; D002248:Carbon Monoxide / Q000494:pharmacology; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology*; D004373:Ductus Arteriosus / Q000502:physiology; D005260:Female; D008027:Light; D008797:Metyrapone / Q000494:pharmacology; D011247:Pregnancy; D012756:Sheep; D014661:Vasoconstriction; D014680:Veins / Q000196:embryology* / Q000502:physiology
D065607:Cytochrome P-450 Enzyme Inhibitors; D002248:Carbon Monoxide; D003577:Cytochrome P-450 Enzyme System; D008797:Metyrapone