Assessment of Relationship of Serum Neurokinin-B Level in the Pathophysiology of Pre-eclampsia: A Case-Control Study.

INTRODUCTION: Pre-eclampsia is a pregnancy-induced disorder that complicates approximately 5-7% of pregnancies. It is the leading cause of maternal and foetal morbidity and mortality worldwide. AIM: To determine the role of serum neurokinin-B level in the pathophysiology of pre-eclampsia. METHODS: This was a case-control study. A total of 80 pregnant women in their third trimester of pregnancy were included in the study. They were divided into two groups (40 pre-eclamptic and 40 normotensive) according to the presence or absence of clinical parameters of pre-eclampsia. Serum level of neurokinin-B was measured with ELISA. RESULTS: Maternal age, weight, BMI, pulse, systolic BP and diastolic BP were statistically higher in the pre-eclampsia group compared to the normotensive group (P < 0.0001). Moreover, statistically higher levels were observed for neurokinin-B in the normotensive group as compared to the pre-eclamptic group. The mean value of neurokinin-B was 83.50 ng/L in the pre-eclamptic group compared to 111.5 ng/L in the normotensive group (P = 0.006). CONCLUSION: Higher levels of serum neurokinin-B were observed in the normotensive pregnant females as compared to the pre-eclamptic females. Thus, apparently, it seems that serum neurokinin-B plays no role in the pathophysiology of pre-eclampsia, and further large multicentre prospective studies may be required to ascertain its role.

The usefulness of circulating levels of leptin, kisspeptin, and neurokinin B in obese girls with precocious puberty.

This study investigated the relationships of circulating leptin, kisspeptin, and neurokinin B (NKB) levels with precocious puberty (PP) in overweight/obese girls and evaluated the usefulness of these markers in the initiation of puberty. One hundred and twenty-eight girls aged 7.0-8.9 years with PP (group A, normal-weight; group B, overweight/obese) and 30 age-matched normal controls (NC) were enrolled. Serum levels of leptin, kisspeptin, and NKB were measured by commercial kits. Serum leptin levels were higher in group A (4.21 ng/mL) and B (5.64 ng/mL) compared to the NC (2.35 ng/mL, p < .001). Serum kisspeptin levels were lower in group A (0.59 ng/mL) than in group B (0.66 ng/mL, p = .018). Serum NKB levels were not different among the three groups. The predictive value of leptin (AUC =0.791) was lower than that of IGF-1 (AUC =0.917, p = .009), although both were significant markers for PP in the regression analysis. BMI z-score (AUC =0.806) was a predictive factor of PP. In conclusion, a higher level of leptin, IGF-1, and fatness in overweight/obese girls with PP compared to the NC confirms their roles in the regulation of puberty. Further research is needed if the effects of kisspeptin and NKB on puberty are limited at the levels of neurons or target tissue.

KNDy neurone activation prior to the LH surge of the ewe is disrupted by LPS.

In the ewe, steroid hormones act on the hypothalamic arcuate nucleus (ARC) to initiate the GnRH/LH surge. Within the ARC, steroid signal transduction may be mediated by estrogen receptive dopamine-, ß-endorphin- or neuropeptide Y (NPY)-expressing cells, as well as those co-localising kisspeptin, neurokinin B (NKB) and dynorphin (termed KNDy). We investigated the time during the follicular phase when these cells become activated (i.e., co-localise c-Fos) relative to the timing of the LH surge onset and may therefore be involved in the surge generating mechanism. Furthermore, we aimed to elucidate whether these activation patterns are altered after lipopolysaccharide (LPS) administration, which is known to inhibit the LH surge. Follicular phases of ewes were synchronised by progesterone withdrawal and blood samples were collected every 2 h. Hypothalamic tissue was retrieved at various times during the follicular phase with or without the administration of LPS (100 ng/kg). The percentage of activated dopamine cells decreased before the onset of sexual behaviour, whereas activation of ß-endorphin decreased and NPY activation tended to increase during the LH surge. These patterns were not disturbed by LPS administration. Maximal co-expression of c-Fos in dynorphin immunoreactive neurons was observed earlier during the follicular phase, compared to kisspeptin and NKB, which were maximally activated during the surge. This indicates a distinct role for ARC dynorphin in the LH surge generation mechanism. Acute LPS decreased the percentage of activated dynorphin and kisspeptin immunoreactive cells. Thus, in the ovary-intact ewe, KNDy neurones are activated prior to the LH surge onset and this pattern is inhibited by the administration of LPS.

Basal Serum Neurokinin B Levels in Differentiating Idiopathic Central Precocious Puberty from Premature Thelarche.

OBJECTIVE: To find out the diagnostic role of kisspeptin and neurokinin B in idiopathic central precocious puberty (ICPP) and premature thelarche (PT). METHODS: The girls who presented with early breast development before the age of 8 years were evaluated. Patients with intracranial pathologies were excluded. Basal and stimulated follicle-stimulating hormone/luteinizing hormone (LH) levels and basal neurokinin B/kisspeptin levels were measured. Patients who had peak value of LH >5 mIU/mL and a bone age (BA)/chronological age (CA) ratio >1.1 were diagnosed as central precocious puberty (CPP), while cases who did not meet these criteria were diagnosed as PT. Healthy age-matched prepubertal girls were included as the control group. RESULTS: The study group contained 25 girls with ICPP (7±0.8 years), 35 girls with PT (6.8±0.7 years), and 30 controls (6.7±0.7 years). Basal serum kisspeptin and neurokinin B levels were 2.36±0.47 ng/mL and 2.61±0.32 ng/mL, respectively in the ICPP group, 2.23±0.43 ng/mL and 2.24±0.23 ng/mL, respectively in the PT group, and 1.92±0.33 ng/mL and 2.03±0.24 ng/mL, respectively in the controls. Both kisspeptin and neurokinin B levels were higher in the ICPP and PT groups compared to controls (p<0.05). Moreover, basal neurokinin B level was different between ICPP and PT groups (p<0.01). A serum neurokinin B level of 2.42 ng/mL provided the most appropriate level to differentiate ICPP from PT, with a sensitivity of 84% and specificity of 77.1%. CONCLUSION: Differentiation of CPP from PT is sometime difficult, and there is a need for a simple method for the differential diagnosis. Our results suggest that basal serum neurokinin B level can be used as an adjunctive parameter to differentiate ICCP from PT.

Identifying late-onset fetal growth restriction by measuring circulating placental RNA in the maternal blood at 28 weeks' gestation.

BACKGROUND: Late-onset fetal growth restriction (FGR) is often undetected prior to birth, which puts the fetus at increased risk of adverse perinatal outcomes including stillbirth. OBJECTIVE: Measuring RNA circulating in the maternal blood may provide a noninvasive insight into placental function. We examined whether measuring RNA in the maternal blood at 26-30 weeks' gestation can identify pregnancies at risk of late-onset FGR. We focused on RNA highly expressed in placenta, which we termed "placental-specific genes." STUDY DESIGN: This was a case-control study nested within a prospective cohort of 600 women recruited at 26-30 weeks' gestation. The circulating placental transcriptome in maternal blood was compared between women with late-onset FGR (<5th centile at >36+6 weeks) and gestation-matched well-grown controls (20-95th centile) using microarray (n = 12). TaqMan low-density arrays, reverse transcription-polymerase chain reaction (PCR), and digital PCR were used to validate the microarray findings (FGR n = 40, controls n = 80). RESULTS: Forty women developed late-onset FGR (birthweight 2574 ± 338 g, 2nd centile) and were matched to 80 well-grown controls (birthweight 3415 ± 339 g, 53rd centile, P < .05). Operative delivery and neonatal admission were higher in the FGR cohort (45% vs 23%, P < .05). Messenger RNA coding 137 placental-specific genes was detected in the maternal blood and 37 were differentially expressed in late-onset FGR. Seven were significantly dysregulated with PCR validation (P < .05). Activating transcription factor-3 messenger RNA transcripts were the most promising single biomarker at 26-30 weeks: they were increased in fetuses destined to be born FGR at term (2.1-fold vs well grown at term, P < .001) and correlated with the severity of FGR. Combining biomarkers improved prediction of severe late-onset FGR (area under the curve, 0.88; 95% CI 0.80-0.97). A multimarker gene expression score had a sensitivity of 79%, a specificity of 88%, and a positive likelihood ratio of 6.2 for subsequent delivery of a baby <3rd centile at term. CONCLUSION: A unique placental transcriptome is detectable in maternal blood at 26-30 weeks' gestation in pregnancies destined to develop late-onset FGR. Circulating placental RNA may therefore be a promising noninvasive test to identify pregnancies at risk of developing FGR at term.

[Effects of obesity on peak level of luteinizing hormone in gonadotropin-releasing hormone agonist test and obesity-related hormones in girls with central precocious puberty].

OBJECTIVE: To explore the effects of obesity on the peak level of luteinizing hormone (LH) in the gonadotropin-releasing hormone (GnRH) agonist test and obesity-related hormones in girls with central precocious puberty (CPP). METHODS: Three hundred and thirty-three girls with CPP who underwent the GnRH agonist test between 2012 and 2014 were classified into three groups: normal weight (n=123), overweight (n=108), and obesity (n=102), according to body mass index (BMI). The sexual development indices were compared between the three groups. Twenty girls were randomly selected from each group for evaluation of the serum levels of leptin, sex hormone binding globulin (SHBG), neurokinin B, and kisspeptin. The correlation of BMI with the levels of various hormones was assessed using Pearson correlation analysis. RESULTS: There was no significant difference in mean age at diagnosis between the three groups; however, the bone age was significantly higher in the overweight and obesity groups than in the normal weight group (P<0.05). The peak level of LH in the GnRH agonist test and SHBG level in the normal weight group were significantly higher than those in the overweight and the obesity groups, while the serum levels of leptin and neurokinin B were significantly lower in the normal weight group than in the overweight and the obesity groups (P<0.05). BMI was negatively correlated with the peak level of LH in the GnRH agonist test and SHBG level (P<0.05), and positively correlated with the levels of leptin and neurokinin B (P<0.05). CONCLUSIONS: The effects of BMI on the result of the GnRH agonist test and levels of obesity-related hormones should be taken into account in girls with precocious puberty.

Serum neurokinin B levels in newly diagnosed nondipper hypertensive patients.

OBJECTIVE: Cardiovascular diseases are more common in patients with nondipper hypertension (NDHT) compared with those with dipper hypertension (DHT). The aim of this study is to evaluate the serum neurokinin B levels in DHT and NDHT patients. METHODS: The study population included newly diagnosed hypertensive patients who were not under antihypertensive treatment. A total of 77 patients were evaluated with ambulatory blood pressure monitoring and divided into two groups: NDHT (n=42) and DHT (n=35). Plasma neurokinin B levels were measured using the ELISA method. RESULTS: Serum neurokinin B levels were significantly higher in the NDHT group compared with the DHT group [254 (180-888) and 207 (116-752) pg/ml, respectively; P=0.024]. There is a positive correlation between the mean night-time systolic blood pressure and plasma neurokinin levels (r=0.590; P<0.001). On regression analysis, neurokinin B level was only found to be related to the mean night-time systolic blood pressure (unstandardized ß=-22.02±9.59; P<0.001). CONCLUSION: Plasma neurokinin B level is higher in patients with NDHT, indicating an unfavorable cardiovascular prognosis. There is a need for further studies that search for the relation between serum neurokinin B levels and NDHT.

Plasma urotensin II and neurokinin B levels in acute myocardial infarction and stable coronary artery disease.

OBJECTIVE: This aim of the study is to investigate whether there are possible plasma urotensin-II (U-II) and neurokinin B (NKB) level changes in patients with acute myocardial infarction (AMI) or not and plasma urotensin-II (U-II) and neurokinin B (NKB) level changes in patients with acute myocardial infarction (AMI) and stable coronary artery disease (CAD) and to evaluate whether there is any relationship between these changes and the pathogenesis of these diseases. METHODS: This is a prospective case-control study. Three groups were formed from randomly admitted patients with AMI, stable CAD, and controls. Biochemical parameters and U-II and NKB levels were measured. Patients with congestive heart failure, chronic hepatic and renal failure, severe cardiac valve disease, and severe pulmonary hypertension were excluded from the study. The normality of the data was evaluated using the Kolmogorov-Smirnov test. We compared the three groups with one-way ANOVA and Tukey test (Kruskal-Wallis test and Mann-Whitney U test). RESULTS: Compared with controls (n=31) and CAD patients (n=32), AMI patients (n=32) had lower U-II and NKB levels. In cases of stable CAD, U-II and NKB levels were similar. A positive correlation was found between U-II and NKB (r=0.720; p=0.000). U-II and NKB were poorly correlated with left ventricle ejection fraction but not with C-reactive protein. CONCLUSION: We found that U-II and NKB levels were lower in patients with AMI in than those with CAD or the control group. According to our findings, the decreased U-II and NKB levels were related to complicated atherosclerotic events.

Significance of serum neurokinin B and kisspeptin levels in the differential diagnosis of premature thelarche and idiopathic central precocious puberty.

The aim of the present study was to investigate the diagnostic role of serum neurokinin B level and its relationship with kisspeptin and leptin, which are known to be involved in the initiation of pubertal process. Girls who presented with breast development (<8 years) were included in the study. All patients underwent bone age assessment. Basal levels of serum follicle stimulating hormone and luteinizing hormone were measured and gonadotropin releasing hormone stimulation test was performed. Patients with a bone age/chronological age ratio >1 and a peak luteinizing hormone response in gonadotropin releasing hormone stimulation test >5mIU/L were included in the central precocious puberty group, while patients who did not meet these criteria were included in the premature thelarche group. Patients with organic pathologies were excluded. Healthy prepubertal girls with similar age were included as the control group. Leptin, kisspeptin and neurokinin B levels were measured by ELISA method. The study included 20 girls with idiopathic central precocious puberty 22 girls with premature thelarche and 24 prepubertal controls. While serum kisspeptin, leptin and neurokinin B levels were significantly higher in central precocious puberty and premature thelarche groups compared to controls, no significant difference was found between central precocious puberty and premature thelarche groups. Increased serum levels of leptin, kisspeptin and neurokinin B in patients with premature thelarche and central precocious puberty suggest that they take part during the initiation of pubertal process, however, these markers are not able to differentiate patients with central precocious puberty from premature thelarche.

Neurokinin B and pre-eclampsia: a decade of discovery.

At the start of the last decade, we provided evidence that levels of the peptide neurokinin B were highly elevated in pre-eclampsia. We hypothesized that elevated levels of neurokinin B may be an indicator of pre-eclampsia and that treatment with certain neurokinin receptor antagonists may be useful in alleviating the symptoms. At the time of the original hypothesis many questions remained outstanding. These included - Does neurokinin B have any diagnostic value in the detection and diagnosis of pre-eclampsia? - What is the cause of the elevated levels of neurokinin B during pre-eclampsia? - What is the physiological significance of neurokinin B in the placenta? This review discusses the answers to these questions taking into account the subsequent developments of the past ten years and analyzing the plethora of discoveries that have arisen from those initial observations.

Neurokinin B and urotensin II levels in pre-eclampsia.

OBJECTIVE: To verify neurokinin B (NKB) and urotensin II (UII) plasma levels in pre-eclampsia (PE) and to determine the relationship between plasma NKB and UII levels. METHOD: A total of 60 women in the third trimester of pregnancy were recruited, 40 women with PE (study patients) and 20 age- and BMI-matched normotensive women (healthy controls). They were divided into three groups: the 20 normotensive pregnant women (Group 1); 20 women with mild PE (Group 2); 20 women with severe PE (Group 3). The plasma levels of NKB and UII were measured simultaneously by enzyme-linked immunosorbent assay. RESULTS: Compared with controls, levels of NKB were significantly higher in women with mild or severe PE (p < 0.01 for both groups), levels of UII were significantly higher in women with mild or severe PE (p < 0.01 for both groups). Moreover, there was a positive correlation between plasma levels of NKB and UII in pre-eclamptic women (r = 0.783, p < 0.01). CONCLUSIONS: These findings suggest that there was an elevation of NKB and UII in the plasma of pre-eclamptic women. NKB and UII may be involved in the pathophysiology of PE and associated with the development of severe disease.

[Relationship between neurokinin B and endothelin-1 and hypertensive disorders complicating pregnancy].

OBJECTIVE: To investigate the relationship between neurokinin B (NKB), endothelin-1 (ET-1) and the pathogenesis of hypertensive disorder complicating pregnancy (HDCP). METHODS: 22 HDCP, who received antenatal examination in the Department of Obstetrics and Gynecology of Union Hospital of Tongji Medical College in Huazhong University of Science and Technology from March to July in 2005, were selected for the study, including 12 gestational hypertension (gestational hypertension group) and 10 preeclampsia (preeclamptic group); 22 normal pregnant women in the same period were served as control. At different gestational weeks, maternal plasma levels of NKB and ET-1 in three groups were detected by enzyme-linked immunoassay technique, the expression and location of NKB in placenta were examined by immunohistochemical SP, and mRNA expressions of NKB and ET-1 in placenta were measured with RT-PCR method. RESULTS: (1) At 10 - 14, 20 - 24, and 30 - 34 gestational weeks, the plasma levels of NKB and ET-1 in preeclamptic group were (35.6 +/- 5.2), (17.9 +/- 4.3), (39.5 +/- 4.3), (22.7 +/- 3.6), (47.1 +/- 3.3) and (27.5 +/- 3.5) microg/L, respectively; in the control group they were (22.9 +/- 3.3), (10.7 +/- 5.3), (30.2 +/- 3.4), (13.2 +/- 4.1), (34.6 +/- 4.3) and (16.6 +/- 4.8) microg/L, respectively. There was a significant difference between preeclamptic group and control group (P < 0.05), while there was no significant difference between gestational hypertension group and control group (P > 0.05). (2) Immunohistochemical staining for NKB protein was observed in all groups and was located in the villous syncytiotrophoblast and villous vascular endothelial cells as well as cytoplasm of stromal cells, mostly located in villous syncytiotrophoblast. The expressions of NKB in placenta of preeclamptic group (0.244 +/- 0.020) was significantly higher than that in control group (0.160 +/- 0.012), with a significant difference between the two groups (P < 0.05). However, there was no significant difference between gestational hypertension group (0.162 +/- 0.019) and control group (P > 0.05). (3) The transcription levels of the NKB mRNA (0.97 +/- 0.36) and ET-1 mRNA (0.90 +/- 0.36) in preeclamptic placentas were both significantly higher than those in control groups (0.78 +/- 0.54, 0.65 +/- 0.47, respectively), with a significant difference between the two groups (P < 0.05). But there was no significant difference between gestational hypertension group (0.80 +/- 0.40, 0.70 +/- 0.32, respectively) and control group (P > 0.05). (4) There was an evident positive correlation between plasma NKB and ET-1 levels in preeclampsia (r = 0.79, P < 0.05). CONCLUSIONS: The significantly increased maternal plasma levels of NKB and ET-1 of patients with preeclampsia occur at early pregnancy (10 - 14 gestational weeks) before the onset of clinical symptoms. The change of maternal plasma levels of NKB and ET-1 is closely related to pathogenesis of HDCP.

Third trimester plasma neurokinin B levels in women with and without preeclampsia.

OBJECTIVE: This study was undertaken to measure neurokinin B (NKB) levels in pregnant women with and without preeclampsia (PE) in the third trimester. The study focused on the Black (sub-Saharan ancestry) and 'mixed ancestry' (synonymous with 'colored' and denotes an established race group of Khoisan, European, Malay, Malagascan, African, and South Indian ancestry) populations, constituting the majority of inhabitants of the Western Cape Province of South Africa. METHODS: Questionnaires were used to obtain clinical data from pregnant 'mixed ancestry' and Black women. Third trimester plasma NKB levels were determined by enzyme-linked immunosorbent assay technique (EIA) in 72 pregnant women with PE and in 94 healthy women. The EIA results were then correlated with clinical data. RESULTS: The mean NKB concentration in the PE groups (23.5 ng/L for 'mixed ancestry' and 15.0 ng/L for Black women) was significantly higher than in the control groups (3.8 ng/L and 4.4 ng/L, respectively; p < or = 0.001). No significant differences in maternal clinical data were found between the diseased groups. CONCLUSIONS: Using the EIA technique, this study confirms previous reports of elevated NKB levels in the plasma of PE women in the third trimester. Whether increased NKB levels are causative or merely associated with PE remains unknown, as do the causative molecular mechanisms. Future longitudinal studies are certainly needed to further elucidate the predictive value of NKB in PE.

Neurokinin B levels in maternal and umbilical cord blood in preeclamptic and normal pregnancies.

Neurokinin (NK) B has been recently demonstrated to be secreted by the placenta in preeclampsia suggesting it may modulate pathophysiological events of the disease. The aim of this study was to investigate whether NKB is the circulating factor associated with preeclampsia or not. In 22 preeclamptic and normotensive pregnant women, the peripheral and umbilical cord blood NKB levels were measured by radioimmunoassay. The NKB levels in women with preeclampsia were 0.70 (0.53-0.92) nmol/L in peripheral blood and 1.92 (1.42-2.35) nmol/L in umbilical cord blood. In normotensive pregnant women, NKB levels were 0.43 (0.29-0.61) nmol/L and 0.14 (0.07-0.33), respectively. Significantly higher levels of NKB were measured in preeclamptic women compared with normotensive pregnant women in umbilical cord blood. These results suggest that NKB enters both fetal and maternal circulation and may modulate fetoplacental hemodynamics.

Altered plasma neurokinin B levels in patients with pre-eclampsia.

OBJECTIVE(S): This study determines the levels of Neurokinin B (NKB) in the plasma of South African coloured pregnant women with and without preeclampsia (PE) and correlates these results with clinical data. Additionally, the peptide radioimmunoassay (RIA) and peptide enzyme immunoassay (EIA) methods were compared in the determination of the Neurokinin B levels, using 58 samples from patients with PE. METHODS: At the Tygerberg Hospital, Cape Town, SA, 43 pregnant women with PE and 62 healthy pregnant women were recruited, and clinical data were gathered using questionnaires; 58 patient samples were tested by both RIA and EIA. RESULTS: The comparison of RIA and EIA revealed an r-value of 0.904. The mean NKB concentration in the PE group (23.5 ng/l) was significantly higher than in the control group (3.8 ng/l). Within the PE cohort, two NKB subgroups could be discerned: those with levels <30 ng/l and those with levels >30 ng/l. CONCLUSION(S): This study, carried out within a distinct population, confirms previous reports of elevated NKB levels in the plasma of pre-eclamptic women in the third trimester, and established the suitability of EIA for determining NKB levels. Whether the altered NKB levels are causative or merely associated with PE still remains to be determined. The split in the two NKB groups (high and low values) needs further evaluation, as does whether NKB could be used as a screening test or as a predictive factor.

Neurokinin B and nitric oxide plasma levels in pre-eclampsia and isolated intrauterine growth restriction.

OBJECTIVE: To verify if neurokinin B plasma level is increased in pre-eclampsia and IUGR. Also, to ascertain if there is a correlation between neurokinin B plasma level and nitric oxide production. DESIGN: A total of 90 pregnant women were studied. Thirty had a gestation complicated by pre-eclampsia and 30 by isolated IUGR; the other 30 were controls. In all patients, neurokinin B plasma level and nitric oxide metabolites (nitrites/nitrates) level were measured. SETTING: University, General Hospital, Messina, Italy. METHODS: Neurokinin B blood samples were taken at 33.5 weeks of gestation and at term. Samples for nitric oxide breakdown products were taken at delivery from the antecubital vein and then from the umbilical vein. RESULTS: Neurokinin B plasma levels in the pre-eclamptic and IUGR groups were significantly higher than controls. Nitric oxide metabolites levels in pre-eclamptic and IUGR patients were also higher than controls. Regression analysis showed a significant correlation among neurokinin B plasma values and nitric oxide metabolite levels either in pre-eclampsia, in IUGR or in the control group. CONCLUSION: Neurokinin B could be involved in pregnancy haemodynamic adaptation via nitric oxide production. In pregnancies complicated with pre-eclampsia and IUGR, increased neurokinin B plasma level, correlated well with increased nitric oxide metabolite level, which may be a compensatory mechanism to improve blood flow to the uteroplacental unit.

Neurokinin B levels in maternal circulation during early pregnancy.

Neurokinin B levels were measured between the 10th-20th weeks of pregnancy, i.e., prior to the development of clinical symptoms, in women who developed preeclampsia or delivered a growth-restricted baby. No difference was found in plasma neurokinin B levels, although neurokinin B levels increased slightly towards term.

Neurokinin B peptide serum levels are higher in normotensive pregnant women than in preeclamptic pregnant women.

OBJECTIVES: The purpose of this study was to examine neurokinin B levels in serum from preeclamptic and normotensive and to investigate the role of neurokinin B in preeclampsia. STUDY DESIGN: Peripheral and uterine venous blood neurokinin B levels were measured in 14 normotensive and 8 preeclamptic pregnant women by radioimmunoassay. RESULTS: Neurokinin B levels in normotensive women were 4.91 +/- 2.67 nmol/L in peripheral and 5.59 +/- 2.06 nmol/L in uterine blood. In pregnant women with preeclampsia, neurokinin B levels were 2.79 +/- 1.68 nmol/L and 3.20 +/- 1.55 nmol/L, respectively. Neurokinin B levels were significantly higher in normotensive women (P=.032 in peripheral and P=.006 in uterine blood). CONCLUSIONS: Neurokinin B serum levels were higher in normotensive women. Higher neurokinin B concentrations in normotensive pregnant women may be due to the advanced gestational age and/or the result of a negative interaction of other vasoactive substances. The role of neurokinin B in preeclampsia remains to be determined.

Neurokinin B is a paracrine vasodilator in the human fetal placental circulation.

Neurokinin (NK) B is a member of the tachykinin family of neurotransmitters, exerting hypotensive or hypertensive effects in the mammalian vasculature through synaptic release from peripheral neurons, according to either NK(1) and NK(2) or NK(3) receptor subtype expression, respectively. There is recent evidence that NKB is expressed by the syncytiotrophoblast of the human placenta, an organ that is not innervated. We hypothesized that NKB is a paracrine modulator of tone in the fetal placental circulation. We tested this hypothesis using the in vitro perfused human placental cotyledon. Our data show that NKB is a dilator of the fetal vasculature, causing a maximal 25.1 +/- 4.5% (mean +/- SEM; n = 5) decrease in fetal-side arterial hydrostatic pressure (5- microM NKB bolus; effective concentration in the circulation, 1.89 nM) after preconstriction with U-46619. RT-PCR demonstrated the presence of mRNA for NK(1) and NK(2) tachykinin receptors in the placenta. Using selective receptor antagonists, we found that NKB-induced vasodilation is through the NK(1) receptor subtype. We found no evidence for the involvement of either nitric oxide or prostacyclin in this response. This study demonstrates a paracrine role for NKB in the regulation of fetal placental vascular tone.

Profile of neurokinin B concentrations in maternal and cord blood in normal pregnancy.

OBJECTIVE: Neurokinin B (NKB) is a neuropeptide with a vasopressor effect belonging to the tachykinin family. This neuropeptide has attracted attention since recent reports indicated that it is also secreted in the placenta and is probably a cause of pre-eclampsia. To provide a basis for elucidation of the relationship between pre-eclampsia and NKB, this study aimed to clarify the trend of changes in blood NKB levels during normal pregnancy by measuring NKB concentrations in maternal blood during various gestational periods and in umbilical blood. METHODS: Fifty-nine normal pregnant women, 12 normal puerperal women and 24 nonpregnant women were studied. The normal pregnant women comprised of 24 at 8-20 weeks' gestation (early), 11 at 28-34 weeks (middle) and 24 at 35-40 weeks (late). Plasma was separated from peripheral blood samples, umbilical venous blood samples (n = 24) and umbilical arterial blood samples (n = 9). Peptide fractions were extracted from each plasma sample and NKB concentrations were measured by the radioimmunoassay method. RESULTS: The NKB concentration in early pregnancy was not significantly different from that in the nonpregnant state. During pregnancy, the blood NKB concentration increased with advance in gestational week, and a correlation was demonstrated by a linear regression equation. The concentration during puerperium was significantly lower than that in late pregnancy. The umbilical blood concentration was significantly higher than the maternal blood concentration in late pregnancy. There was no significant difference between umbilical venous and arterial blood. CONCLUSION: This study demonstrated that NKB secreted from the placenta during pregnancy enters both the maternal and fetal circulation. These results suggest that NKB may modulate fetoplacental haemodynamics through a paracrine mechanism.