Nitric oxide metabolites in cervical fluid during pregnancy:: Further evidence for the role of cervical nitric oxide in cervical ripening

OBJECTIVE: Cervical tissue expresses all the isoenzymes of nitric oxide synthase. We studied the concentrations of nitric oxide metabolites in the cervical fluid in nonpregnant (n = 11) and pregnant women (n = 106). STUDY DESIGN: Cervical fluid was collected into a Dacron polyester swab, and nitric oxide metabolites were eluted into physiologic saline solution, which was assayed for nitric oxide metabolites with the Griess reaction. The detection limit of the method is 0.2 mumol/L. RESULTS: Cervical fluid nitric oxide metabolite was detectable in, 46% of nonpregnant women (median, < 0.2 mumol/L; 95% Cl, 0-49), in 63% of women in early pregnancy (median, 11 mumol/L; 95% Cl, 0-23) and in 82% of women in late pregnancy (median, 128 mumol/L; 95% Cl, 21-276). In late pregnancy, the cervical fluid nitric oxide metabolite level was higher in women with Bishop score of greater than or equal to6 (median, 163 mumol/L; 95% Cl, 105-276) than in women with Bishop score of <6 (median, 86 mumol/L; 95% Cl,21-99). Cervical fluid nitric oxide metabolite concentration before the onset of labor in parous women (median, 97 mumol/L; 95% Cl, 78-283) was higher (P = .008) than that in nulliparous women (median, 28 mumol/L; 95% Cl, 0-95). Cervical fluid nitric oxide metabolites before the initiation of labor (median, 33 mumol/L; 95% Cl, 0-95) rose to 3.5-fold (median, 115 mumol/L; 95% Cl, 78-284) after the commencement of uterine contractions and showed a significant relationship to Bishop score (r = 0.39, P = .01). Cervical fluid nitric oxide metabolite concentrations were not relative to simultaneous plasma nitric oxide metabolite levels (n = 41 women, r = 0.14, P =.41). Rupture of fetal membranes tended to decrease cervical fluid nitric oxide metabolite levels, whereas gentle cervical manipulation elevated it 6.6-fold in 1 minute. The administration of glyceryl trinitrate (0.5 mg, nitric oxide donor) intracervically resulted in a significant rise in the cervical fluid nitric oxide metabolite level in 2 minutes. CONCLUSION: Cervical fluid nitric oxide metabolite level rises after cervical ripening, nitric oxide donor administration, or cervical manipulation, which supports a role for cervical nitric oxide in cervical ripening.