Properties of an endogenous arachidonic acid--elicited relaxing mechanism in human placental vessels.
OBJECTIVE
Our objective was to examine the action of arachidonic acid on tone in isolated human placental arteries and veins (1 to 2 mm diameter) for mechanisms involving endothelium-derived mediators, the stimulation of guanylate cyclase, and prostaglandin and cytochrome P450 metabolites.


METHODS
Pharmacologic probes and endothelium-removal were used to examine the mechanism of relaxation to arachidonic acid (10 nmol/L to 10 mumol/L) observed in placental arteries and veins obtained after delivery from uncomplicated term pregnancies and precontracted with prostaglandin F2 alpha.


RESULTS
Neither removal of the endothelium nor inhibition of prostaglandin biosynthesis with 10 mumol/L indomethacin, arginine-derived nitric oxide formation with 30 mumol/L nitro-L-arginine, or guanylate cyclase stimulation with 10 mumol/L LY83583 altered the observed relaxation to arachidonic acid in either preparation. However, this relaxation was markedly attenuated by 30 mumol/L proadifen (SKF-525A), an inhibitor of cytochrome P450, suggestive of a role for arachidonic acid metabolism by an epoxygenase or monooxygenase pathway.


CONCLUSIONS
Human placental arteries and veins possess an endogenous mechanism of relaxation to arachidonic acid, which seems to be mediated by metabolites formed by a cytochrome P450 enzyme. This endogenous relaxation mechanism could function as a suppressor of vasospasm in the placental circulation.
Omar
H A
HA
Department of Physiology, New York Medical College, Valhalla 10595.
Figueroa
R
R
Omar
R A
RA
Wolin
M S
MS
D016718:Arachidonic Acid / Q000494:pharmacology / Q000502:physiology*; D001120:Arginine / Q000378:metabolism; D001808:Blood Vessels / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D006152:Cyclic GMP / Q000378:metabolism; D004730:Endothelium, Vascular / Q000502:physiology; D005260:Female; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism; D010920:Placenta / Q000098:blood supply*; D011247:Pregnancy; D011335:Proadifen / Q000494:pharmacology; D014664:Vasodilation / Q000502:physiology*
D016718:Arachidonic Acid; D009569:Nitric Oxide; D001120:Arginine; D011335:Proadifen; D006152:Cyclic GMP