natriuretic-peptide--c-type and Pre-Eclampsia

In the last three decades many members of the natriuretic peptide family was isolated. The function and physiological role of these peptides are pleiotropic. All natriuretic peptides are synthesized from polypeptide precursors. Together with the sympathetic nervous system and other hormones they play key roles, like an endogenous system in the regulation of the body fluid homeostasis and blood pressure. Changes in this balance lead to dysfunction in the endothel and left ventricle, which can cause severe complications. In many cardiovascular diseases natriuretic peptides serve not only as marker for diagnosis and prognosis but they have therapeutic importance. In the last years the potential use of the elevated BNP levels for diagnosis of pre-eclampsia was examined. In our review we discuss the current understanding of molecular biology, biochemistry and clinical relevance of natriuretic peptides.

Topics: Atrial Natriuretic Factor; Biomarkers; Blood Pressure; Cardiovascular Diseases; Female; Humans; Liver Cirrhosis; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Natriuretic Peptides; Pre-Eclampsia; Pregnancy; Renal Insufficiency; Shock, Septic; Tissue Distribution

To evaluate serum levels of the amino-terminal propeptide of C-type natriuretic peptide (NTproCNP) in uneventful pregnancies and pregnancies complicated by preeclampsia (PE) and NTproCNP's accuracy for prediction of PE.. Nested case control pilot study including women with uneventful pregnancy (Control, n = 100) and asymptomatic women who later developed PE (PE_long, n = 12). NTproCNP levels were measured in a maximum of ten sequential blood samples per patient (seven visits during pregnancy, three afterwards), which had been collected prospectively.. In controls, NTproCNP decreased from weeks 11-13 on, reaching a nadir at the end of the second trimester (weeks 23-27), and subsequently reached the highest levels at the end of pregnancy. In comparison, the PE_long group showed a significantly different NTproCNP course (p = .042), including significantly elevated levels in weeks 18-22 (p = .034) and 23-27 (p = .016). Significant predictive power of single time point measurements of NTproCNP for predicting short-term occurrence of preeclampsia in asymptomatic women was found in weeks 28-32 (p = .023) and 33-36 (p = .014). Furthermore, an increase > -0.038 pmol/l per week between weeks 11-13 and 14-17 was also predictive for PE (area under the curve, AUC: 0.75; p < .001; sensitivity: 90%; specificity: 60%), as was an increase of > 0.084 pmol/l per week between weeks 11-13 and 18-22 (AUC: 0.69, p = .048; sensitivity: 55%; specificity: 88%).. Measurement of NTproCNP in pregnancy might be useful to increase diagnostic awareness in women who will develop PE.

Topics: Adult; Biomarkers; Case-Control Studies; Female; Humans; Natriuretic Peptide, C-Type; Pilot Projects; Pre-Eclampsia; Predictive Value of Tests; Pregnancy; Prospective Studies

To determine changes in plasma C-type natriuretic peptide (CNP), a paracrine product of the vascular endothelium, in pregnancies with vascular disorders, and relate these to time of presentation and severity.. Retrospective nested cases and controls.. Community study, Auckland New Zealand.. Screening for Pregnancy Endpoints (SCOPE) data and bio-bank of maternal plasma.. Maternal plasma amino terminal proCNP (NTproCNP) was measured by radioimmunoassay in early (14-16 weeks of gestation, and again at 19-21 weeks of gestation) and late (34-36 weeks of gestation) pregnancy in three groups of women (20 per group): pre-eclampsia (pre-eclampsia); gestational hypertension (GHT) with small for gestational age (SGA); and uncomplicated pregnancy.. Change in NTproCNP and associations with concurrent blood pressure, time of case presentation, severity, and infant birthweight.. Plasma NTproCNP in early pregnancy in women with vascular disorders did not differ from those found in controls. In late pregnancy, levels in pre-eclampsia (28.8 ± 2.3 pM) and in GHT with SGA (28.6 ± 4.8 pM) were significantly increased (P = 0.01 and 0.027, respectively) compared with controls (21.3 ± 1 pM). In pre-eclampsia, levels were significantly higher (P < 0.03) at 14-16 weeks of gestation in women diagnosed prior to 34 weeks of gestation. Combining all three groups, associations of NTproCNP with concurrent diastolic and mean arterial pressure were found at 34-36 weeks of gestation (r = 0.46). No significant associations were identified with birthweight.. CNP secretion during gestation is responsive to vascular stress. Plasma NTproCNP measurements may have clinical application in late pregnancy in defining the different phenotypes associated with pre-eclampsia.

Topics: Adult; Biomarkers; Birth Weight; Blood Pressure; Case-Control Studies; Female; Fetal Growth Retardation; Humans; Infant, Small for Gestational Age; Natriuretic Peptide, C-Type; New Zealand; Phenotype; Pre-Eclampsia; Pregnancy; Prognosis; Retrospective Studies

We have identified recently a new peptide, NT-proCNP(1-50) (N-terminal pro-C-type natriuretic peptide), in the circulation of humans and sheep. A previous report of an elevated fetal-maternal gradient in immunoreactive CNP raised the possibility that processing and metabolism of proCNP may differ in maternal and fetal tissues. We therefore collected matching peripheral maternal and umbilical cord plasma samples at delivery from women with normotensive and pre-eclamptic pregnancies to investigate the presence and concentrations of CNP and NT-proCNP using HPLC and RIA. Plasma concentrations of NT-proCNP in normotensive umbilical cord plasma were 10-fold higher than maternal venous levels (246+/-17 compared with 24.3+/-1.8 pmol/l; P <0.001) and much higher than corresponding levels of CNP (3.6+/-0.4 compared with 1.8+/-0.3 pmol/l in the fetal and maternal plasma respectively; P <0.001). Although there was no significant difference between normotensive and pre-eclamptic plasma CNP concentrations in either maternal or umbilical cord blood, NT-proCNP showed a significant statistical interaction ( F =5.8, P =0.025) between the source (maternal or fetal) and gestational group (normotensive or pre-eclamptic). Maternal NT-proCNP levels were raised in the pre-eclampsia group, whereas the converse was observed in umbilical cord blood. In conclusion, the greatly elevated ratio of NT-proCNP/CNP in fetal compared with maternal plasma suggests that synthesis, as well as clearance, of CNP (but not NT-proCNP clearance) are markedly increased in fetal tissues.

Topics: Adult; Female; Fetal Blood; Humans; Natriuretic Peptide, C-Type; Placenta; Pre-Eclampsia; Pregnancy

One of the fundamental issues in pre-eclampsia (hypertension in pregnancy) research is to find serum proteins that can act as markers of disease predisposition, remote disease onset, imminent disease onset or disease activity at the height of its destructive powers. We make assumptions, not infrequently, that positive findings at the time of delivery reflect early changes in the maternal and fetal circulations. Very little has been defined in terms of fetal circulation, as it is, by and large, deemed to be harder to access and less likely to lend itself to useful non-invasive diagnostic tests in early pregnancy. The study published in this issue of Clinical Science by Prickett et al. shows that there is a differential expression of the precursor molecule of CNP (C-type natriuretic peptide), N-terminal proCNP, in pre-eclampsia. At term, pre-eclamptic umbilical cord plasma concentrations are decreased relative to normal pregnancy, possibly reflecting a decrease in placental production. At the same time maternal levels are increased relative to normal pregnancies and this possibly reflects an increase in myometrial/endovascular production. There is no doubt that the predominant actions of these hormones are local and whether plasma levels are a true reflection of dynamic changes in local production and effect is yet to be seen. This study represents a promising start in identifying large stable molecules which could be markers for pre-eclampsia. This study has relatively small numbers of patients and work still needs to be done to determine the utility of umbilical cord levels in early phases of the disease. Whether serum levels of N-terminal proCNP can provide an accurate reflection of normal or pathological maternal uterine adaptation to pregnancy remains a question worth evaluating.

Topics: Biomarkers; Female; Fetal Blood; Humans; Natriuretic Peptide, C-Type; Pre-Eclampsia; Pregnancy

To measure plasma levels of C-type natriuretic peptide in women with normal pregnancies and those complicated by gestational hypertension and preeclampsia.. We collected venous plasma samples from 20 women with normal pregnancies, 15 with gestational hypertension, and nine with preeclampsia. Gestational ages ranged from 26-39 weeks. We measured C-type natriuretic peptide concentrations by radioimmunoassay. Statistical comparisons were made by one-way analysis of variance and Tukey test.. The mean plasma concentration of C-type natriuretic peptide in the women with normal pregnancy was 7.1 +/-2.5 pg/mL, in those with gestational hypertension 9.6+/-4.2 pg/mL, and in those with preeclampsia 8.1+/-2.4 pg/mL. There were no statistically significant differences between groups. The statistical power to detect a difference of 3 pg/mL at the 5% significance level was 78% for the group with gestational hypertension and 64% for the preeclamptic group.. Our results suggest that C-type natriuretic peptide plasma levels are not significantly different in normal pregnancies and those complicated by gestational hypertension or preeclampsia. In hypertensive pregnancy disorders, C-type natriuretic peptide showed a distinct course compared with atrial natriuretic peptide and brain natriuretic peptide.

Topics: Adult; Female; Gestational Age; Humans; Hypertension; Natriuretic Peptide, C-Type; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Cardiovascular; Radioimmunoassay