cyclic-gmp and Birth-Weight

The higher risk of respiratory problem in infants delivered by elective caesarean section in comparison with vaginally born infants may be favoured by lower level of nitric oxide (NO) and carbon monoxide (CO) and higher oxidative stress in infants born by caesarean section. We studied healthy term infants born by vaginal delivery or by elective caesarean section. Nitric oxide, CO, guanosine 3-5 cyclic monophosphate, total hydroperoxide and advanced oxidation protein products (AOPP) were measured at birth and 48-72 h of life. Nitric oxide, CO and cGMP were lower at birth and at 48-72 h of life in infants born by elective caesarean delivery. Total hydroperoxide and AOPP levels were similar in the two groups and increased from birth to 48-72 h of life. In conclusion, nitric oxide and CO concentrations were higher in term infants vaginally born than in infants born by elective caesarean section and decreased from birth to 48-72 h of life. The mode of delivery did not affect the oxidative stress which increases from birth to 48-72 h of life.

Topics: Birth Weight; Carbon Monoxide; Cyclic GMP; Humans; Hydrogen Peroxide; Infant, Newborn; Nitric Oxide; Oxidative Stress; Reference Values

The Nitric Oxide (NO) system plays an important role in the establishment and maintenance of the feto-placental circulation. Research on the pathogenesis of preeclampsia in several studies has established the involvement of the NO-system in preeclampsia and fetal intrauterine growth restriction (IUGR). In the presented study we analyzed the urine and plasma concentrations of nitrite/nitrate, the stable endproducts of NO and its second messenger, cyclic Guanosinemonophosphate (cGMP) in normal, preeclamptic and IUGR pregnancies.. In total 76 patients were investigated in a prospective study for repeated determination of plasma and urinary levels of nitrate/nitrite and cGMP: 49 patients with a normal course of pregnancy, 14 patients with fetal IUGR and 13 patients with preeclampsia were included into the study. Plasma and urine Nitrite/Nitrate-concentrations were determined using a Colorimetric Assay (Cayman Inc., USA), concentrations of the second messenger cGMP in plasma and urinary samples were determined with a J(125)-Radio-Immuno-Assay (ibl Inc., Germany). The Stat View Program (Abacus Concepts, Inc., Berkeley, CA, 1992-1998) was used for statistical analysis, a P value <0.05 was considered significant.. Analyzing the data with the Kruskall-Wallis test a significance was reached for Plasma Nitrite/Nitrate (P=0.0236), plasma cGMP (P=0.004) and urinary nitrite/nitrate (P=0.032). No significance was seen for urinary cGMP (P=0.656). Comparing normal and preeclamptic and normal and IUGR pregnancies the following significant differences were seen (Mann-Whitney U test): In preeclamptic pregnancies urine nitrite/nitrate concentration was significantly lower compared to normal pregnancies (P=0.009) No significant difference between normal and preeclamptic pregnancies for plasma nitrite/nitrate (P=0.819) and plasma-cGMP (P=0.072) could be observed. In IUGR pregnancies plasma nitrite/nitrate and the plasma-cGMP concentrations were both significantly lower compared to normal pregnancies (P=0.0077 and 0.0066) in IUGR-pregnancies. No significance was reached when analyzing urine-Nitrite/Nitrate (P=0.7).. Whereas in preeclampsia a reduced urinary nitrite/nitrate was analyzed, IUGR pregnancies showed reduced plasma nitrite/nitrate and cGMP. A reduced release of NO into the maternal circulation might lead to the presented findings and be involved in the pathogenesis of preeclampsia and fetal IUGR.

Topics: Birth Weight; Cyclic GMP; Female; Fetal Growth Retardation; Humans; Infant, Newborn; Nitrates; Nitric Oxide; Nitrites; Pre-Eclampsia; Pregnancy; Pregnancy Outcome; Prospective Studies

During pregnancy, CRH and CRH-related peptides appear to regulate the fetoplacental circulation via activation of the nitric oxide (NO)/cGMP pathway. Pregnancies with abnormal placental function such as preeclampsia (PE) are characterized by increased maternal plasma CRH concentrations and reduced placental CRH-receptor 1alpha (CRH-R1alpha) expression. In this study, we investigated the actions of CRH/CRH-related peptides on the NO/cGMP system in normal and PE placentas (n = 8 for each group). Fluorescent in situ hybridization, RT-PCR, and immunofluorescence experiments in human term placenta detected mRNAs expression for both R1 and R2 types of CRH-R, as well as urocortin (UCN) II and UCN III and showed CRH-R protein expression mainly in syncytiotrophoblast, whereas the endothelial NO synthase (eNOS) expression was confined within the cytoplasm of the chorionic villi. In placental explants, CRH and UCN induced mRNA and protein expression of eNOS, but not inducible NOS, and also caused an acute increase in cGMP levels (maximal stimulation, 80-90% above basal; P < 0.05). UCN II also induced a modest induction of cGMP (42% above basal; P < 0.05). These responses were attenuated by the NOS and soluble guanylyl cyclase inhibitors, l-N(G)-nitro-l-arginine methyl ester and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one. In PE placental explants there was a significant reduction in CRH/CRH-related peptide-induced cGMP response; however, changes in the mRNA content of eNOS, inducible NOS, and soluble guanylyl cyclase (assessed by quantitative RT-PCR) between normal and PE placentas were not altered. In conclusion, we demonstrated that CRH and CRH-related peptides can positively regulate the placental NO/cGMP system. This pathway appears to be impaired in PE and may contribute toward dysregulation of the balance controlling vascular resistance.

Topics: Adolescent; Adult; Birth Weight; Blood Pressure; Cesarean Section; Corticotropin-Releasing Hormone; Cyclic GMP; Female; Humans; Infant, Newborn; Nitric Oxide; Parity; Peptides; Placenta; Pre-Eclampsia; Pregnancy; Receptors, Corticotropin-Releasing Hormone; Reverse Transcriptase Polymerase Chain Reaction

In chronically hypertensive (CH), preeclamptic (PE), and normotensive pregnant women (N), we investigated ex vivo platelet aggregation in response to L-arginine (L-Arg) and sodium nitroprusside (SN), which are respectively the substrate and donor of nitric oxide (NO).. Platelet aggregation was determined with a dual-channel aggregometer by measuring transmittance of light through the sample in comparison to platelet poor plasma, as a reference. Aggregation induced by adenosine diphosphate was continuously recorded for 3 min and measured before and after preincubation with L-Arg and SN.. Preincubation with L-Arg significantly reduced platelet aggregation in N and CH patients (p < 0.05) but not in PE women. Preincubation with SN affected aggregation in PE women also (p < 0.001). No correlation was found between platelet response to L-Arg or SN stimuli and the severity of hypertensive disorders expressed as week of gestation at delivery or birth weight.. The present study demonstrates that a decreased platelet sensitivity to L-Arg characterizes PE women, whereas SN maintains its antithrombotic power. This impairment seems to be specific for PE, because platelets of CH patients utilize L-Arg normally. This finding supports the involvement of the L-Arg-NO pathway in the pathogenesis of the procoagulative features of PE and probably in the onset of the disease. The maintained response to SN in PE patients suggests a possible therapeutical use of NO donors in the disease.

Topics: Adult; Analysis of Variance; Antihypertensive Agents; Arginine; Birth Weight; Blood Pressure; Case-Control Studies; Cesarean Section; Chronic Disease; Cross-Sectional Studies; Cyclic GMP; Female; Gestational Age; Humans; Hypertension; Nitric Oxide Donors; Nitroprusside; Platelet Aggregation; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Cardiovascular; Statistics, Nonparametric

To elucidate the role of the L-arginine:nitric oxide pathway in pregnancy and pre-eclampsia.. Pregnant women (nulliparous, age <25 years). Normotensive pregnancy (n=22) was defined when blood pressure remained at levels of <120/80 mmHg and there was no proteinuria. Women with pre-eclampsia (n=22) had blood pressure measurements of >140/90 mmHg and proteinuria of >300 mg/l. Nonpregnant normotensive women (n=22) were studied as controls.. Blood samples were taken for measurements of ionised calcium, atrial natriuretic factor, cyclic guanosine 3'5' monophosphate (GMP),arginine and asymmetric dimethylarginine. Urine samples were collected for determination of cyclic GMP excretion. Cyclic GMP concentrations were also determined in 12 women with severe pre-eclampsia before and after treatment with hydralazine.. L-arginine, asymmetric dimethylarginine and atrial natriuretic factor were not different in any group. Cyclic GMP concentrations in plasma [0.94 (SD 0.23) nM] as well as in urine [50.1 (SD 15.7) microM] were increased significantly (P<0.05) in normal pregnancy compared to nonpregnant controls [plasma mean 0.46 (SD 0.12) nM and urine mean 18.4 (SD 10.3) microM], but not in the pre-eclampsia group [plasma mean 0.48 (SD 0.10) nM and urine mean 24.1 (SD 14.5) microM]. Concentrations of cyclic GMP in plasma and urine increased significantly (P<0.05) in women treated with hydralazine.. The differences in cyclic GMP concentrations may reflect differences in nitric oxide production. Hydralazine increases cyclic GMP concentrations in severely pre-eclamptic women. This action could explain the antihypertensive effect of hydralazine.

Topics: Adult; Arginine; Birth Weight; Blood Pressure; Cyclic GMP; Female; Humans; Hydralazine; Nitric Oxide; Pre-Eclampsia; Pregnancy; Vasodilator Agents

This study has used an in vitro perfusion method to investigate the mechanism by which CRH causes vasodilatation in the human fetal-placental circulation. In normal term placentas, vasodilatory responses to human CRH (24-7000 pmol/L) were examined during submaximal vasoconstriction (100-120 mm Hg) of the fetal-placental vasculature induced by prostaglandin F2 alpha (0.7-2 mumol/L), KCl (50-100 mmol/L), or the thromboxane A2 mimetic, U46619 (0.05-0.5 mumol/L). Infusion of CRH caused a concentration-dependent vasodilatation that was similar in the presence of each constrictor agent (P > 0.05). The CRH antagonist, alpha-helical CRH-(9-41) (200 pmol/L), and a polyclonal CRH antiserum significantly inhibited CRH-induced vasodilatation during constriction with prostaglandin F2 alpha (P < 0.05). Vasodilatory responses to CRH were attenuated by the nitric oxide synthase inhibitor, N omega-nitro-L-arginine (100 mumol/L; P < 0.05), and the guanylate cyclase inhibitor, LY 83583 (1 mumol/L; P < 0.05), but not by the cyclooxygenase inhibitor, indomethacin (3 mumol/L; P > 0.05). In placentas of women with increased fetal vascular resistance, as demonstrated by Doppler ultrasound waveforms in vivo, CRH-induced vasodilatation was significantly reduced (P < 0.05). These results indicate that in the human fetal-placental circulation, CRH causes a vasodilatory response via a nitric oxide-/cGMP-dependent pathway. CRH may play a role in the control of vascular resistance to blood flow in the normal human placenta, and there may be a deficiency in the CRH signaling pathway of placentas with increased fetal vascular resistance.

Topics: Adult; Birth Weight; Corticotropin-Releasing Hormone; Cyclic GMP; Diabetes, Gestational; Dinoprost; Dose-Response Relationship, Drug; Female; Fetal Growth Retardation; Fetus; Humans; In Vitro Techniques; Infant, Newborn; Maternal-Fetal Exchange; Muscle, Smooth, Vascular; Nitric Oxide; Placenta; Potassium Chloride; Pregnancy; Pregnancy Complications; Reference Values; Regression Analysis; Signal Transduction; Vascular Resistance; Vasoconstriction; Vasodilation