PROPERTIES OF A LACTATE-INDUCED RELAXATION IN HUMAN PLACENTAL ARTERIES AND VEINS

OBJECTIVE: Our purpose was to determine the vasoactive effects and mec hanism of action of lactate in human placental vessels by means of iso metric muscle bath studies. STUDY DESIGN: Isolated 1 to 2 mm human pla cental arteries and veins from normal term pregnancies, precontracted with prostaglandin F2alpha and incubated under a Po2 of approximately 35 torr were exposed to lactate, 1 to 10 mmol/L, (pH 7.4), pyruvate, h ydrogen peroxide, nitroglycerin, or forskolin. The effects of endothel ium removal or inhibitors of cyclooxygenase (indomethacin 10 mumol/L) and L-arginine metabolism (nitro-L-arginine 30 mumol/L) on the respons e to lactate and the effects of an antagonist of guanylate cyclase act ivation (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-depe ndent relaxation was not inhibited by endothelium removal, indomethaci n, or nitro-L-arginine but was attenuated by methylene blue, cyanide, and hypoxia. Relaxation to hydrogen peroxide was inhibited by methylen e blue and cyanide but not hypoxia. Relaxation to nitroglycerin was in hibited only by methylene blue, and relaxation to forskolin was not in hibited by these probes. Pyruvate did not produce a significant relaxa tion. CONCLUSIONS: These findings suggest that lactate causes relaxati on in the human placental vessels by an oxygen and cyclic guanosine 3' :5'-monophosphate-dependent mechanism, which may involve the generatio n of hydrogen peroxide but not the metabolism of arginine. Lactate-ind uced dilatation may be of importance during labor and in situations of acute and chronic fetal hypoxia.