INVOLVEMENT OF A NITRIC OXIDE-CYCLIC GUANOSINE-MONOPHOSPHATE PATHWAY IN CONTROL OF HUMAN UTERINE CONTRACTILITY DURING PREGNANCY

OBJECTIVES: The aims of the study were to investigate whether a nitric oxide-cyclic guanosine monophosphate relaxation pathway is present in the human uterus and whether it differentially inhibits contractility during pregnancy and labor. STUDY DESIGN: Myometrial strips were obtained from pregnant women who were either in labor or not in labor and from nonpregnant women. Nitrites and cyclic guanosine monophosphate production by the tissues and contractile responses to nitric oxide modifiers were measured. RESULTS: Biochemical assays revealed that nitric oxide (nitrites) and cyclic guanosine monophosphate are generated by the human uterus. Cyclic guanosine monophosphate production by the uterus was increased by L-arginine (the substrate for nitric oxide) and diethylamine/nitric oxide (a nitric oxide donor) and decreased by nitro-L-arginine methyl ester (an inhibitor of nitric oxide synthase). Spontaneous contractility in vitro was increased by nitro-L-arginine methyl ester and decreased by diethylamine/nitric oxide, which furthermore produced a dose-dependent inhibition of contractility, and the median effective dose of inhibition in tissues from nonlaboring pregnant patients (1.5 +/- 0.4 mu mol/L) is substantially lower than in tissues from laboring pregnant (21.7 +/- 7.4 mu mol/L or nonpregnant (20.8 +/- 4.4 mu mol/l) women. These studies show that the nitric oxide-cyclic guanosine monophosphate system exists in the human uterus and that it inhibits contractility. Furthermore, the relaxation responsiveness to nitric oxide is elevated during pregnancy and decreased during labor. CONCLUSION: A nitric oxide-cyclic guanosine monophosphate relaxation pathway is present in the human uterus and may be responsible for maintaining uterine quiescence during pregnancy. A decrease in uterine relaxation responsiveness to nitric oxide at term may play a role in the initiation of labor.