Increased serum levels of nitric oxide metabolites among users of levonorgestrel-releasing implants [corrected] a possible role in progestin-induced bleeding.

BACKGROUND: Nitric oxide (NO) is a potent angiogenic and vasodilator factor that could be involved in progestin-induced bleeding. This study aimed to assess possible changes in the serum levels of NO metabolites in users of levonorgestrel-releasing implants (LNG-implants) [corrected] and to identify any correlation between some of their clinical characteristics and NO metabolite levels. METHODS: This cross-sectional study included 37 LNG-implants [corrected] users; a single 5 ml venous blood was collected at different periods of [corrected] use. Women were divided into users with acceptable menstrual bleeding (n 5 13) [corrected] and those having abnormal bleeding patterns (n 5 24) [corrected] The controls are 13 age-matched healthy women; they were fertile, had regular menstruation and did not use any contraceptive method in the previous 3 months. NO was determined by the evaluation of its oxidation products (nitrites and nitrates) where the nitrates were reduced to nitrites with cadmium filings; total serum concentrations of nitrites were measured by using the Griess reaction. RESULTS: The mean serum levels of NO metabolites were significantly higher in the LNG-implants [corrected] users than in the controls (mean+/-SE) 34.9+/-11.3 versus 6.1+/-1.5 mumol/l (P<0.001) [corrected] The mean serum levels of NO metabolites were significantly higher in the LNG-implants [corrected] users with abnormal bleeding patterns than in those with normal bleeding patterns (mean+/-SE) 41.3+/-7.4 versus 23.2+/-5.8 mumol/l (P<0.001) [corrected] There was a positive correlation between NO levels and both prolonged spotting and heavy/prolonged bleeding days (P<0.001 and P<0.01, respectively) and negative correlation between NO levels with the duration of use and length of the menstrual cycle (P<0.05). CONCLUSION: The significantly increased serum levels of NO metabolites among LNG-implants [corrected] users may primarily reflect an increase in its endometrial production, possibly secondary to its increased liberation by systemic vascular endothelium. This may result in enhanced endometrial angiogenesis and vascular dilatation which can induce and perpetuate abnormal excessive/prolonged uterine bleeding.

Placental nitric oxide synthase (NOS) activity and nitric oxide (NO) production in normal pregnancy, pre-eclampsia and eclampsia.

OBJECTIVES: To measure nitric oxide synthase (NOS) activity and total nitrites levels (as an index of nitric oxide 'NO' production) in placental villous homogenate of normal, pre-eclamptic and eclamptic pregnant women. DESIGN: Two groups were studied cross-sectionally: late pregnant women with pre-eclampsia and eclampsia (n=31) and normal pregnant women (all late) as controls (n=32). Two tissue blocks of whole placenta, each 1 x 1 x 1 cm, were collected at delivery and assayed for NOS activity and total nitrite levels. SETTING: Department of Obstetrics and Gynecology, Assiut University Hospitals, Egypt. METHODS: Placental tissues were homogenized and villous homogenates were assayed for NO production by Griess reaction which measures the combined oxidation products for NO (nitrites and nitrates) after reduction with nitrate reductase. NOS activity was determined by measuring NO synthesis by tissue extracts spectrophotometrically using the oxidation of oxyhemoglobin to methemoglobin by NO. RESULTS: Placental villous homogenates of pregnancies complicated by pre-eclampsia and eclampsia had significantly higher NOS activity and total nitrites levels compared with those of normal pregnancy [for NOS (P<0.0001) and for total nitrites (P<0.001)]. CONCLUSIONS: (1) Placental NOS activity and NO production are significantly increased in pre-eclampsia and eclampsia than those of normal pregnancy; this increase was directly related to the severity of this disorder. (2) Such increase possibly represents a physiologic adaptive response to overcome the increased placental vascular resistance and to minimize platelet and leukocyte adhesion to the surface of placental villi or within the intervillous spaces.

Maternal and fetal serum nitric oxide (NO) concentrations in normal pregnancy, pre-eclampsia and eclampsia.

OBJECTIVES: To measure the maternal and fetal serum concentrations of total nitrites and nitrates (as an index of nitric oxide production) in normal pregnancy, pre-eclampsia and eclampsia. DESIGN: Three groups of women were studied cross-sectionally: late pregnant women with pre-eclampsia and eclampsia (n=31); normal late pregnant women (n=32); and age-matched healthy non-pregnant women (n=21). Venous blood samples were collected from all women and both maternal and umbilical venous samples were collected from pregnant women. METHODS: Blood samples were assayed for nitric oxide (NO) production by Greiss reaction which measures the combined oxidation products of NO (total nitrites and nitrates). RESULTS: There was a significant increase in serum total nitrites and nitrates concentrations in normal pregnant women than in the serum of age-matched normal non-pregnant women (P<0.0001). Significantly higher total nitrites and nitrates levels were found in the maternal sera of the pre-eclamptic and eclamptic women compared with those of normal pregnant women (P<0.0001). Also, fetal blood levels of total nitrites and nitrates were significantly increased in pre-eclampsia and eclampsia compared with those of normal pregnancy (P<0.0001). CONCLUSIONS: (1) Serum nitric oxide (NO) production is increased in normal pregnancy than in the normal non-pregnancy. (2) Maternal and fetal serum NO levels are increased significantly in pre-eclampsia and eclampsia, which possibly represents a compensatory/protective mechanism to maintain blood flow and limit platelets aggregation in the fetal-maternal circulations. (3) The increase in NO production is directly related to the severity of pre-eclampsia; this would be of diagnostic significance for the prediction of the severity of this syndrome.