Properties of a lactate-induced relaxation in human placental arteries and veins.
OBJECTIVE
Our purpose was to determine the vasoactive effects and mechanism of action of lactate in human placental vessels by means of isometric muscle bath studies.


METHODS
Isolated 1 to 2 mm human placental arteries and veins from normal term pregnancies, precontracted with prostaglandin F2 alpha and incubated under a PO2 of approximately 35 torr were exposed to lactate, 1 to 10 mmol/L, (pH 7.4), pyruvate, hydrogen peroxide, nitroglycerin, or forskolin. The effects of endothelium removal or inhibitors of cyclooxygenase (indomethacin 10 mumol/L) and L-arginine metabolism (nitro-L-arginine 30 mumol/L) on the response to lactate and the effects of an antagonist of guanylate cyclase activation (methylene blue 10 mumol/L), cyanide (1 mmol/L), and hypoxia (PO2 8-10 torr) on responses to all agents were determined by analysis of variance and t test statistics.


RESULTS
Lactate-elicited dose-dependent relaxation was not inhibited by endothelium removal, indomethacin, or nitro-L-arginine but was attenuated by methylene blue, cyanide, and hypoxia. Relaxation to hydrogen peroxide was inhibited by methylene blue and cyanide but not hypoxia. Relaxation to nitroglycerin was inhibited only by methylene blue, and relaxation to forskolin was not inhibited by these probes. Pyruvate did not produce a significant relaxation.


CONCLUSIONS
These findings suggest that lactate causes relaxation in the human placental vessels by an oxygen and cyclic guanosine-3':5'-monophosphate-dependent mechanism, which may involve the generation of hydrogen peroxide but not the metabolism of arginine. Lactate-induced dilatation may be of importance during labor and in situations of acute and chronic fetal hypoxia.
Omar
H A
HA
Department of Physiology, New York Medical College, Valhalla 10595.
Figueroa
R
R
Tejani
N
N
Wolin
M S
MS
D000704:Analysis of Variance; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001158:Arteries; D005576:Colforsin / Q000494:pharmacology; D003486:Cyanides / Q000494:pharmacology; D015237:Dinoprost / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D005260:Female; D006162:Guanylate Cyclase / Q000502:physiology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007773:Lactates / Q000494:pharmacology*; D019344:Lactic Acid; D008751:Methylene Blue / Q000494:pharmacology; D019335:Nitroarginine; D005996:Nitroglycerin / Q000494:pharmacology; D010100:Oxygen / Q000494:pharmacology; D010920:Placenta / Q000098:blood supply*; D011247:Pregnancy; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology; D011773:Pyruvates / Q000494:pharmacology; D019289:Pyruvic Acid; D014661:Vasoconstriction / Q000187:drug effects*; D014680:Veins
D003486:Cyanides; D007773:Lactates; D011773:Pyruvates; D005576:Colforsin; D019335:Nitroarginine; D019344:Lactic Acid; D019289:Pyruvic Acid; D001120:Arginine; D015237:Dinoprost; D006861:Hydrogen Peroxide; D011451:Prostaglandin-Endoperoxide Synthases; D006162:Guanylate Cyclase; D005996:Nitroglycerin; D010100:Oxygen; D008751:Methylene Blue; D007213:Indomethacin