Nitric Oxide–Mediated Effects on Myometrial Contractility at Term During Prelabor and Labor

Abstract

In Brief Objective To assess the existence of a nitric oxide (NO) system in the human myometrium and the effects of mediators of this system on contractile activity in vitro. Methods Myometrial tissue was obtained before the onset of labor and during labor at term. Production of NO was assessed by the use of nicotinamide dinucleotide phosphate diaphorase staining and by immunoblots for NO. Effects of NO were examined by adding L-arginine (the substrate for NO synthesis); NG-nitro-L-arginine methyl ester (an inhibitor of NO synthase); two NO donors, sodium nitroprusside and spermine NONOate; as well as 8-bromo cyclic guanosine monophosphate (8-bromo cGMP) (a second messenger analogue) to organ baths. Results Myometrial NO production was indicated by positive nicotinamide adenine dinucleotide phosphate diaphorase staining. Immunoblots detected endothelial NO synthase, whereas only a weak signal for inducible NO synthase was seen. The addition of L-arginine (10−4–10−3 mol/L) did not result in any change of contractility. NG-nitro-L-arginine methyl ester (10−3 mol/L) caused a minor increase of contractility in half of the specimens. Sodium nitroprusside, spermine NONOate, and 8-bromo cGMP resulted in a concentration-dependent inhibition of contractility (10−7–10−6 mol/L for sodium nitroprusside, 10−6–10−5 mol/L for spermine NONOate, and 10−5–10−3 mol/L for 8-bromo cGMP). However, at 10−5–10−4 mol/L, sodium nitroprusside exhibited a dose-dependent increase in the frequency of contractions. Women in prelabor did not differ from those in active labor. Conclusion The myometrium produces NO at term. Nitric oxide inhibits myometrial contractile activity. The responsiveness to NO is similar in nonlaboring and laboring women. Nitric oxide synthase is present in human myometrial tissue, and nitric oxide–donating substances inhibit spontaneous contractility of myometrial strips.