PLASMA CONCENTRATIONS AND CORRELATIONS OF NATRIURETIC PEPTIDES AND OXYTOCIN DURING LABOR AND EARLY POSTPARTUM PERIOD.

CONTEXT: Natriuretic peptides (NP) and oxytocin (OT) play an important role in cardiovascular and hydro-electrolytic homeostasis. Changes in NP levels and their roles in cardiovascular adaptations in pregnancy and labor have not been clear. OBJECTIVE: The present study aimed to investigate the changes and correlations in plasma levels of atrial natriuretic peptide (ANP), C-type natriuretic peptide (CNP), B-type natriuretic peptide (BNP) and OT during labor and the postpartum period. STUDY DESIGN: Blood samples were collected from 29 healthy pregnant women in the active phase of spontaneous labor, 15 minutes after delivery and 3 hours postpartum. Plasma levels of OT and the stable N-terminal fragments of NPs (NT-proANP, NT-proCNP, NT-proBNP) were measured using enzyme or electrochemiluminescence immunoassays. RESULTS: The plasma levels of NT-proANP and NT-proCNP significantly decrease 3 hours postpartum compared to the active phase of labor and to 15 minutes after delivery. The plasma NT-proBNP levels significantly higher after delivery and 3 hours postpartum compared to the active phase of labor. A significant correlation exists between OT and NT-proANP levels during the active phase of labor and 15 minutes after delivery. CONCLUSIONS: The data show that during labor and postpartum, the plasma concentrations of the NPs change differently. Elevations in NT- proBNP after delivery suggest that BNP may be involved in postpartum adaptations. The correlations between OT and ANP levels indicate that OT may be partly responsible for the increased levels of ANP and may have a role in the modification of the cardiovascular system.

17Beta-estradiol modulates endothelin-1 expression and release in human endothelial cells.

OBJECTIVE: In this study the role of 17beta-estradiol (E2) in the regulation of endothelin-1 (ET-1) mRNA expression and secretion was investigated in cultured human umbilical vein endothelial cells (HUVECs). METHODS: Endothelial cells were either deprived of or treated with 17beta-estradiol (10(-9), 10(-7) M) for 48 h. After the incubation, the effect of E2 on ET-1 gene expression was evaluated by Northern blot analysis. ET-1 release into the media was measured by radioimmunoassay after 6 h of incubation under basal conditions and upon stimulation with thrombin (4 U/ml). In addition, the cyclic guanosine 5'-monophosphate (cGMP) content of cells was assayed by immunoassay. In order to exclude the role of nitric oxide (NO) in E2-induced effects on endothelin-1 gene expression and secretion, nitric oxide synthase (NOS) inhibitor, N-nitro L-arginine methyl ester (1 mM) (L-NAME) was added to the media of some cultures. RESULTS: Incubation of HUVECs with 10(-9) and 10(-7) M E2 for 48 h resulted in a 30 and 47% inhibition of ET-1 mRNA expression, respectively. Incubation with E2 also decreased the basal and thrombin-stimulated ET-1 release while increasing the cGMP content of cells significantly. NOS inhibitor L-NAME increased the release of ET-1 from E2-incubated cells but did not alter the ET-1 release from hormone-deprived cells. However, ET-1 secretion of E2-treated cells were significantly less than the deprived ones. Northern blot analyses also demonstrated that inhibition of NOS only partly attenuated the effect of E2 on ET-1 gene expression. In the presence of L-NAME, treatment with 10(-7) M E2 caused a 12% decrease in ET-1 gene expression. CONCLUSION: The results demonstrate that E2 may play both direct and indirect role in regulation of ET-1 gene expression and production in human endothelial cells. E2-induced increase in NO but decrease in ET-1 production may partly explain the mechanism of the protective effects of the hormone on the cardiovascular system.

Nitric oxide and endothelin relationship in intestinal ischemia/reperfusion injury.

Gastrointestinal mucosal blood flow is dependent on a balanced release of vasoactive substances from endothelium. Nitric oxide (NO) may increase the flow by vasodilatation and/or antiaggregation whereas endothelin (ET) may decrease it by vasoconstriction and aggregation. NO and ET may have counterbalancing effects on each other in tissue damage. In order to test this hypothesis, in this study on rats, L-arginine to increase NO levels and N(G)-nitro-L-arginine methyl esther (L-NAME) to decrease NO levels have been used in an intestinal ischemia/ reperfusion (I/R) injury model and portal vein ET response was evaluated. Lipid peroxidation product measurements and chemiluminescence (CL) studies were also carried out in ileal tissue samples. Intestinal I/R injury caused an increase in portal venous ET levels with levels of 9.4+/-0.5 fmol/ml in sham operation and 14.8+/-1.6 fmol/ml in I/R group. ET level of L-NAME-sh group was lower than that of sham-operated group and also ET level of L-NAME-I/R group was lower than that of I/R group. This yielded the conclusion that inhibition of NO synthesis decreases portal venous ET levels in this model. Increased NO production by L-arginine caused increased ET levels in sham operated groups but this effect was not observed in I/R injury state. This study also showed that inhibition of NO synthesis has a protective role by reducing the reperfusion damage in this model. It is likely that NO and ET have a feedback effect on each other both under physiologic conditions and I/R injury.

Long-term effect of 17beta-estradiol and thrombin on tissue factor pathway inhibitor release from HUVEC.

In spite of the increasing evidence that estrogens have protective effects on the vascular system, the evidence that estrogens may contribute to the risk of thrombosis is still being debated. We investigated the effect of 17beta-estradiol (E2) on tissue factor pathway inhibitor (TFPI) release from of cultured human umbilical vein endothelial cells (HUVEC). In this study HUVEC were harvested by collegenase treatment and cultured in multiwelled plates with medium 199 supplemented with 10% fetal calf serum and antibiotics. The cells were incubated in the presence or absence of E2 (1 and 100 nM) with/without thrombin (4 U/mL) for 6 or 24 hours. After the incubations TFPI level of media were measured by IMUBIND Total Eliza kit. Our results demonstrates that E2 at physiological concentrations decreases the release of TFPI from HUVEC significantly. Thrombin also decreases TFPI antigen levels detected in culture media. When combined with thrombin the effect of estrogen is not visible due the much higher effectivity of thrombin in diminishing TFPI levels. These results show that E2 shifts the hemostatic balance towards the procoagulant phase through lowering the TFPI levels secreted by the endothelium.