Nitric oxide metabolites, cyclic guanosine 3 ',5 ' monophosphate and dimethylarginines during and after uncomplicated pregnancies: a longitudinal study

Objective: In cross-sectional studies, the variability between women may ma sk or deny gestational changes, related to the nitric oxide-cyclic GMP syst em. Therefore, we analyzed longitudinally as markers of this system, the ur inary levels of nitrite+nitrate (NOx), cyclic guanosine 3',5' monophosphate (cGMP) and of the inhibitor of nitric oxide synthase, dimethylarginine (DM A). Study design: Late-afternoon urine samples were obtained from 20 women with uncomplicated pregnancies and nine non-pregnant women. Creatinine conc entrations (mol) were determined with the Jaffe reagent and NOx (mmol) with the Griess reagent after reduction of nitrate. cGMP (mu mol) was determine d in an enzyme immunoassay and DMA (mmol) after solid-phase extraction and liquid chromatography. Trend analyses and (paired) t-tests were done for de tection of time-related differences. Results: The NOx/creatinine (mmol/mol) ratios of the non pregnant women (63.8+/-18.8, S.D.) did not differ from t hose of the pregnant women at the onset of pregnancy (70.5+/-36.4). Over th e entire pregnancy period these ratios declined significantly (P<0.001) and lower values were found at the end of gestation and after birth (49.6+/-22 .4). The cGMP/creatinine (mu mol/mol) and DMA/creatinine ratios (mmol/mol) changed parabolically (P<0.001). The maxima of 68.0+/-19.9 and of 4.95+/-1. 01 were found at week 20 and 16, respectively. These ratios declined to 45. 2+/-17.7 and to 4.03+/-0.83 at the end of gestation but not further during parturition (39.6+/-17.2 and 4.01+/-1.90). The lowest cGMP/creatinine ratio s occurred one month after birth (27.4+/-15.7) while in the non-pregnant wo men the value was 15.3+/-6.2 mu M/M. The lowest DMA/creatinine ratios, meas ured one month after birth (3.41+/-1.28 mmol/mol) were similar to those of the non-pregnant women (3.75+/-0.39 mmol/mol). Positive instead of negative relationships were found between the DMA results and those of the cGMP (P< 0.001) and NOx determinations (P<0.05). Conclusions: (1) The gestational ch anges of the urinary NOx/creatinine and especially of the GMP/creatinine ra tio reflect most likely changes in vascular resistance. (2) Because of the variability of the results between but also within women, these ratios are useless to monitor supposed changes in NO production during parturition. (C ) 1999 Elsevier Science Ireland Ltd. All rights reserved.