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1 Departments of Obstetrics, Gynecology and Reproductive Sciences, and of Cell Biology and Physiology, University of Pittsburgh, and Magee-Womens Research Institute, Pittsburgh, Pennsylvania 15213; and 2 Departments of Physiology and of Obstetrics and Gynecology, University of New Mexico School of Medicine, Albuquerque, New Mexico 87131
We tested the hypothesis that nitric oxide (NO) biosynthesis increases during normal human pregnancy and decreases in preeclampsia. The major metabolites of NO, nitrate and nitrite (NOx), were measured in both the plasma and 24-h urine of women subjected to a reduced NOx diet. In this way, the plasma and urinary levels mainly reflected endogenous production rather than dietary intake. Moreover, we assessed cGMP, a second messenger of NO, in the same samples. Both NOx and cGMP assays were validated in our laboratory. We first conducted a cross-sectional study of nonpregnant women (n = 15), normal pregnant women in the first (n = 9), second (n = 17) and third (n = 22) trimesters, as well as women with preeclampsia (n = 15) and transient hypertension of pregnancy (n = 7). We also performed a serial study in the same women (n = 9) before, during, and after pregnancy. Taken together, the results of the two investigations suggested marked increases in cGMP production especially during the first trimester when the maternal circulation is rapidly vasodilating. In contrast, whole body NO production as estimated by the plasma level and urinary excretion of NOx was not elevated during the first trimester. Finally, unequivocal demonstration of reduced NO biosynthesis in preeclampsia was not forthcoming.
nitric oxide; guanosine 3',5'-cyclic monophosphate; nitrate; human pregnancy; glomerular filtration
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