endothelin-1 and Diabetes--Gestational

We studied the effect of endothelin (ET)-1 on spontaneous contractions and the effects of nimodipine and isradipine on ET-1-induced contractions in myometrial tissue from normal and diabetic pregnant women.. We isolated myometrial strips from seven normal pregnant and seven gestational diabetic women undergoing elective cesarean section at term. Three sets of experimental studies were performed with three myometrial strips obtained from every woman and mounted in organ baths for recording of isometric tension. In the first set, the effect of increasing concentrations of ET-1 (10(-11)-10(-8) M) on spontaneous contractions was recorded. In the second and third sets, effects of increasing concentration of nimodipine (10(-6)-3.10(-5) M) and isradipine (10(-5)-3.10(-4) M), respectively, on contractions following pretreatment with 10(-8) M ET-1 were recorded.. ET-1, beginning from 10(-9) M and 10(-10) M, significantly increased the amplitude of contractions in normal and diabetic strips, respectively. ET-1, beginning from 10(-9) M, also increased the frequency of contractions in normal and diabetic strips. The amplitude of contractions was significantly higher in diabetic strips as compared with normal strips at 10(-9) and 10(-8) M. There was no significant difference in the frequency of contractions between normal and diabetic strips. ET-1 at 10(-8) M also increased the basal tone of all normal and diabetic strips. Nimodipine, beginning from 10(-6) M and 3.10(-6) M, and isradipine, beginning from 10(-5) M and 3.10(-5) M, significantly decreased the amplitude of contractions in normal and diabetic strips, respectively. Nimodipine at 10(-5) M and 3.10(-5) M and isradipine at 3.10(-4) M significantly decreased the frequency of contractions in normal strips. Nimodipine, except at 3.10(-5) M, and isradipine did not significantly decrease the frequency of contractions in diabetic strips.. Gestational diabetes increases ET-1-induced contractile response in human myometrium. The contractile effect of ET-1 in normal and diabetic myometrium is mediated partly by dihydropyridine-sensitive calcium channels since it is significantly reduced by nimodipine and isradipine. The promising data from this study warrant clinical studies on the definitive place of nimodipine and isradipine in the treatment of preterm labor, especially in a diabetic woman, to avoid metabolic complications of beta-mimetic tocolytics.

Topics: Calcium Channel Blockers; Diabetes, Gestational; Endothelin-1; Female; Humans; Isradipine; Myometrium; Nimodipine; Obstetric Labor, Premature; Pregnancy; Reference Values; Uterine Contraction

Topics: Adult; Amniotic Fluid; Birth Weight; Diabetes, Gestational; Endothelin-1; Female; Humans; Infant, Newborn; Pregnancy

Preeclampsia (PE), fetal growth restriction (FGR) and gestational diabetes mellitus (GDM) are major pregnancy complications affecting maternal and fetal health. The placenta and the vasoconstrictor endothelin-1 (ET-1) have a controlling and mediating role in these conditions. This study tested the hypothesis that the expression of ET-1 and its receptors (ET(A) and ET(B)) is altered in these pathologies and differs between early (gestational week [GW] ≤ 34) and late (GW > 34) third trimester pregnancies.. The study included 88 women (GW 28-41) with PE (blood pressure >140/90 mmHg, protein >300 mg/24 hrs; n=14), FGR (<10th birthweight centile and pathological umbilical blood flow; n=13), PE+FGR (n=5) and GDM (n=21), and gestational age-matched controls (n=35). ET-1, ET(A) and ET(B) mRNA and ET(A) and ET(B) protein were quantified in placental tissues by real-time PCR and immunoblotting.. The ET/ETR mRNA system is altered in PE and PE+FGR and GDM. Expression of ET-1, ET(A) and ET(B) is upregulated in early onset PE and PE+FGR with stronger effect in PE+FGR. GDM down regulated ET/ETR mRNA in the placentas in late third trimester of pregnancy. ET/ETR protein is virtually unchanged.. Early onset PE (≤GW34) with or without FGR is associated with increased mRNA expression of the ET/ETR system, while in late onset PE and GDM the opposite effect was observed. This study supports the emerging concept that early and late onset PE are different diseases.

Topics: Adult; Case-Control Studies; Diabetes, Gestational; Down-Regulation; Endothelin-1; Female; Fetal Growth Retardation; Gestational Age; Humans; Placenta; Polymerase Chain Reaction; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, Third; Receptor, Endothelin A; Receptor, Endothelin B; RNA, Messenger; Up-Regulation; Young Adult

Pregnancy complicated by diabetes is associated with increased risk of unfavorable obstetric outcomes. A common abnormality in diabetes is endothelial dysfunction resulting in an altered pattern of vasoactive substance production by the endothelial cells. The aim of study was to assess serum endothelin-1 (ET-1) and cyclic guanosine monophosphate (cGMP) in pregnant women with pregravid (PGDM) or gestational diabetes (GDM).. At the time of delivery, serum ET-1, cGMP, glycated hemoglobin (A1c), fructosamine and non-fasting glucose were measured in 19 PGDM, 23 GDM and 18 controls.. ET-1 and cGMP were similar in all groups. In GDM there was a positive association between A1c and ET-1 (r = 0.437; p < 0.05) and cGMP (r = 0.542; p < 0.02). In the controls, but not in PGDM and GDM, we found a positive correlation between ET-1 and cGMP (r = 0.634; p < 0.005). In women with diabetes, an optimal (A1c <6%) or inadequate (A1c >6%) metabolic control of diabetes did not influence ET-1 or cGMP levels.. In women with PGDM and GDM, serum ET-1 and cGMP were similar to the levels observed in healthy pregnant women. However, the physiological balance between vasoconstrictor and vasodilator substances might be defective in pregnancies complicated by diabetes.

Topics: Blood Glucose; Cyclic GMP; Diabetes, Gestational; Endothelin-1; Female; Fructosamine; Glycated Hemoglobin; Humans; Pregnancy; Pregnancy in Diabetics; Statistics, Nonparametric

We measured plasma concentrations of asymmetric dimethylarginine (ADMA), endothelin-1 (ET-1), soluble vascular cell adhesion molecule-1 (sVCAM-1) and E-selectin in 56 patients with gestational diabetes (GDM), 68 pregnant women with normal glucose tolerance (NGT) and 36 healthy non-pregnant women. ADMA concentrations were markedly lower in NGT [0.48 (0.42-0.55) micromol/l] than in GDM subjects [0.50 (0.43-0.67) micromol/l] and healthy controls [0.57 (0.46-0.72) micromol/l, P = 0.005]. ET-1 levels were comparable between GDM [0.76 (0.58-0.90) pg/ml] and NGT women [0.75 (0.63-0.92) pg/ml] and significantly higher than in the non-pregnant subjects [0.62 (0.52-0.72) pg/ml, P = 0.007 and P = 0.005, respectively]. There were no differences in sVCAM-1 and E-selectin levels between the groups studied. ADMA levels were significantly associated with fasting glucose (beta = 0.23, P = 0.02) and gestational age (beta = 0.24, P = 0.01). Our results suggest that physiological adaptation to pregnancy is associated with a fall in circulating ADMA and an elevation of ET-1 concentrations, irrespective of the disturbances of glucose tolerance.

Topics: Adult; Arginine; Blood Glucose; Case-Control Studies; Diabetes, Gestational; Endothelin-1; Female; Humans; Pregnancy; Vascular Cell Adhesion Molecule-1

The aim of the study was to assess the relationship between maternal and umbilical cord plasma concentrations of endothelin 1 (ET-1) and cyclic guanosine monophosphate (cGMP) in women with diabetes mellitus (DM).. The study was performed on 19 neonates of women with pregestational DM, 23 neonates of women with gestational diabetes (GDM), and 18 neonates of healthy uncomplicated pregnancies.. We found that umbilical and maternal ET-1 and cGMP concentrations in pregestational DM or GDM women were not changed in comparison with the controls. In women without DM, positive correlations between maternal (r=0.64; p<0.005) and umbilical cord plasma (r=0.60; p<0.009) ET-1 and cGMP concentrations were found. However in pregnancies complicated by pregestational DM or GDM such associations were not observed.. Umbilical and maternal plasma concentrations of ET-1 and cGMP in pregnant women with pregestational diabetes as well as gestational diabetes were not changed in comparison with the non-diabetic women. In women without DM maternal and umbilical cord plasma ET-1 and cGMP concentrations showed positive correlations. In pregnancies complicated by pregestational DM or GDM maternal and umbilical cord plasma ET-1 and cGMP concentrations were not interdependent.

Topics: Adult; Cyclic GMP; Diabetes, Gestational; Endothelin-1; Female; Fetal Blood; Humans; Pregnancy; Pregnancy in Diabetics; Risk Factors; Young Adult