15-hydroxy-11-alpha-9-alpha-(epoxymethano)prosta-5-13-dienoic-acid and Pre-Eclampsia

[Figure: see text].

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Adenylyl Cyclase Inhibitors; Adult; Calcium Channel Blockers; Endothelium, Vascular; Female; Humans; Indoles; Kynurenine; Muscle, Smooth, Vascular; Myometrium; Omentum; Peptides; Pre-Eclampsia; Pregnancy; Ryanodine Receptor Calcium Release Channel; Vascular Resistance; Vasoconstrictor Agents; Vasodilation; Vasodilator Agents

l-tryptophan induces IDO (indoleamine 2,3-dioxygenase) 1-dependent vasodilation. IDO1 is expressed in placental endothelial cells and downregulated in preeclampsia. Hypothesizing that this may contribute to diminished placental perfusion, we studied l-tryptophan-induced vasodilation in healthy and early-onset preeclampsia placental arteries, focusing on placental kynurenine pathway alterations. Despite IDO1 downregulation, kynurenine pathway metabolite concentrations (measured with ultra-performance liquid chromatography-tandem mass spectrometry) were unaltered in preeclamptic versus healthy placentas. Most likely, this is due to enhanced l-tryptophan uptake, evidenced by increased l-tryptophan levels in preeclamptic placentas. Ex vivo perfused cotyledons from healthy and preeclamptic placentas released similar amounts of l-tryptophan and kynurenine pathway metabolites into the circulations. This release was not altered by adding l-tryptophan in the maternal circulation, suggesting that l-tryptophan metabolites act intracellularly. Maternally applied l-tryptophan did appear in the fetal circulation, confirming placental passage of this essential amino acid. After in vitro incubation of placental arteries with IDO1-upregulating cytokines interferon-γ and tumor necrosis factor-α, l-tryptophan induced vasodilation. This vasodilation was attenuated by both IDO1 and nitric oxide (NO) synthase inhibitors. Despite IDO1 downregulation, l-tryptophan-induced relaxation was enhanced in preeclamptic versus healthy placental arteries. However, cytokine stimulation additionally upregulated the LAT (l-type amino acid transporter) 1 in preeclamptic placental arteries only. Vasodilation to the lipophilic, transporter independent ethyl ester of l-tryptophan was reduced in preeclamptic versus healthy placental arteries, in agreement with reduced IDO1 expression. In conclusion, l-tryptophan induces IDO1- and NO-dependent relaxation in placental arteries, which is determined by l-tryptophan uptake rather than IDO1 expression. Increased l-tryptophan uptake might compensate for reduced IDO1 expression in preeclamptic placentas.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Adult; Arteries; Carrier Proteins; Cytokines; Enzyme Induction; Female; Humans; Indoleamine-Pyrrole 2,3,-Dioxygenase; Kynurenine; Maternal-Fetal Exchange; Nitric Oxide; Nitric Oxide Synthase; Placenta; Pre-Eclampsia; Pregnancy; RNA, Messenger; Tryptophan; Vasodilation

Preeclampsia (PE) is a pregnancy-related disorder characterized by hypertension and proteinuria that affects 3-10% of all pregnancies. Although its pathophysiology remains obscure, placental hypoxia-induced oxidative stress and alterations in vascular function, morphology, and endothelial barrier integrity are considered to play a key role in the development of preeclampsia. In this study, placental villous explants of noncomplicated placentae and BeWo cells were subjected to hypoxia. The effect of placental hypoxic-conditioned medium (HCM) on intraluminal-induced contraction and endothelial barrier integrity in chorionic arteries was investigated using pressure myography. The impact of BeWo cell HCM on endothelial cell viability, reactive oxygen species formation and inflammation was also determined. Alterations in arterial morphology and contractile responsiveness to the thromboxane A2 analog (U46619) after exposure to placental HCM were examined immunohistochemically and by wire myography, respectively. Intraluminal administration of placental HCM induced vasoconstriction and increased the endothelial permeability for KCl, which was concentration-dependently prevented by quercetin. Placental and BeWo cell HCMs decreased endothelial cell viability, increased the production of reactive oxygen species and enhanced the secretion of IL-6 and IL-8. The cross-sectional area of the arterial media was increased upon exposure to placental HCM, which was associated with increased vascular proliferation and contractile responsiveness to U46619, and all of these effects were prevented by the antioxidants quercetin and RRR-α-tocopherol. This study is the first to comprehensively demonstrate the link between factors secreted by placental cells in response to hypoxia and vascular abnormalities and paves the way for new diagnostic approaches and therapies to better protect the maternal vasculature during and after a preeclampsia-complicated pregnancy.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Cell Line; Culture Media, Conditioned; Endothelial Cells; Endothelium, Vascular; Female; Humans; Hypoxia; In Vitro Techniques; Permeability; Placenta; Pre-Eclampsia; Pregnancy; Reactive Oxygen Species; Vasoconstriction

Preeclampsia is a major health problem in human pregnancy, severely complicating 5-8% of all pregnancies. The emerging molecular mechanism is that conditions like hypoxic stress trigger the release of placental messengers into the maternal circulation, which causes preeclampsia. Our objective was to develop an in vitro model, which can be used to further elucidate the molecular mechanisms of preeclampsia and which might be used to find a remedy.. Human non-complicated term placentas were collected. Placental explants were subjected to severe hypoxia and the conditioned media were added to chorionic arteries that were mounted into a myograph. Contractile responses of the conditioned media were determined, as well as effects on thromboxane-A2 (U46619) induced contractility. To identify the vasoactive compounds present in the conditioned media, specific receptor antagonists were evaluated.. Factors released by placental explants generated under severe hypoxia induced an increased vasoconstriction and vascular contractility to thromboxane-A2. It was found that agonists for the angiotensin-I and endothelin-1 receptor released by placental tissue under severe hypoxia provoke vasoconstriction. The dietary antioxidant quercetin could partially prevent the acute and sustained vascular effects in a concentration-dependent manner.. Both the acute vasoconstriction, as well as the increased contractility to U46619 are in line with the clinical vascular complications observed in preeclampsia. Data obtained with quercetin supports that our model opens avenues for e.g. nutritional interventions aimed at treating or preventing preeclampsia.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Cell Hypoxia; Chorion; Constriction, Pathologic; Culture Media, Conditioned; Endothelium, Vascular; Female; Humans; Hypoxia; Muscle Contraction; Myography; Placenta; Pre-Eclampsia; Pregnancy; Vasoconstriction; Vasoconstrictor Agents

Pre-eclampsia (PE) is associated with vascular endothelial dysfunction and oxidative stress initiated by impaired trophoblast invasion. Oxidative stress modifies circulating low-density lipoprotein (LDL) to oxidized LDL (oxLDL). Lectin-like oxLDL receptor-1 (LOX-1) is a scavenger receptor for oxLDL. We hypothesized that plasma from patients with PE alters LOX-1 in normal human vessels during pregnancy, causing oxLDL-induced impairment of vascular function.. Control-matched plasma was obtained from women with PE (n = 6). Oxidized LDL and soluble LOX-1 levels were determined by enzyme-linked immunoassay (ELISA). Remaining plasma was pooled and stored at -80ºC. Human omental arteries were incubated in 3% plasma from normal pregnant (NP) women or plasma from women with PE. Expression of LOX-1 in these vessels was determined by immunohistochemistry with antibodies against LOX-1. The omental vessels were exposed to oxLDL and the LOX-1 inhibitor TS20. Vascular function was assessed in response to the vasoconstrictor U46619 and the vasodilators bradykinin (BK) and sodium nitroprusside (SNP).. No significant differences in the concentrations of oxLDL or soluble LOX-1 (sLOX-1) were found in plasma from women with PE as compared with NP women. The expression of LOX-1 was not significantly different in either the NP or PE incubated omental vessels. Incubation of vessels from NP women in plasma from women with PE impaired their relaxation in response to BK as compared with that of NP vessels incubated in plasma from NP women. Exposure to oxLDL further impaired relaxation in NP vessels incubated with plasma from women with PE. Inhibition of LOX-1 protected against the impairment of vascular relaxation induced by plasma from women with PE.. Inhibition of LOX-1 prevents endothelial dysfunction in an in vitro model of PE and may prove useful as a therapeutic target in the treatment of PE.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Adult; Arteries; Bradykinin; Case-Control Studies; Endothelium, Vascular; Female; Humans; In Vitro Techniques; Lipoproteins, LDL; Nitroprusside; Omentum; Oxidative Stress; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Cardiovascular; Scavenger Receptors, Class E; Vasoconstrictor Agents; Vasodilator Agents

Control of vascular resistance and blood flow in the fetoplacental circulation is incompletely understood. Reactive oxygen species (ROS), physiological and pathophysiological regulators of vascular tone, are elevated in preeclampsia (PE), a disease of pregnancy characterized by increased fetoplacental vascular resistance. We tested the hypothesis that ROS modulate vascular reactivity in placental chorionic plate arteries. Wire myography was used to examine (1) the effects of acute exposure to ROS on arterial function in normal pregnancy and (2) the effects of maternal antioxidant supplementation on arterial reactivity in women at high risk for PE participating in the Vitamins in Pre-eclampsia (VIP) trial. ROS generated by xanthine plus xanthine oxidase enhanced basal tension, vasoconstriction in response to the thromboxane mimetic U46619, and relaxation in response to sodium nitroprusside. Hydrogen peroxide and peroxynitrite increased basal tone and relaxed preconstricted arteries (U44619), respectively. In women at risk for PE, chorionic plate artery constriction in response to U46619 was greater in the women receiving placebo compared to the women supplemented with the antioxidant vitamins C and E. ROS may regulate fetoplacental vascular resistance and blood flow in the short term, and chronic exposure to raised ROS could contribute to elevated fetoplacental vascular resistance in PE and fetal growth restriction (FGR).

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Adult; Antioxidants; Chorion; Female; Humans; In Vitro Techniques; Myography; Placenta; Placental Circulation; Pre-Eclampsia; Pregnancy; Reactive Oxygen Species; Regional Blood Flow; Umbilical Arteries; Vasoconstriction; Vitamins; Xanthine; Xanthine Oxidase; Young Adult

Agonist-induced tone oscillations (rhythmic contractions and relaxations) occur in vascular beds to allow acute regulation of volume flow and thus the delivery of oxygen and nutrients to the tissue. Mechanisms responsible for the control of human placental vasomotor tone and blood flow are poorly characterized. This study aimed to characterise thromboxane-induced tone oscillations in human placental and myometrial arteries. Chorionic plate and myometrial arteries obtained from biopsies at term were mounted for isometric tension measurement. Tone oscillations were observed in chorionic arteries only when exposed to sub-maximal (<1 microM) concentrations of U46619. Slow (mean+/-SEM) frequency (2.6+/-0.5 per hour), large amplitude (39+/-7% of peak contraction) tone oscillations were elicited by 0.03 microM U46619 (n=18). In the presence of the nitric oxide synthase (NOS) inhibitor l-NNA (100 microM) the amplitude was significantly reduced (40+/-13% to 18+/-8%, P<0.05, n=6), frequency was unaltered and the bradykinin-dependent vasodilator response was reduced (68+/-13% to 40+/-19%, P<0.05, n=6). Myometrial arteries exposed to 1 microM U46619 developed tone oscillations within 10 min, which increased in amplitude over 30min occurring at relatively constant frequency. The mean amplitude of oscillations at 30 min (31+/-7%, n=16) was similar to that in chorionic arteries but the occurrence more frequent (42.8+/-9.7 per hour, P<0.001). Inhibition of NOS did not alter tone oscillations in myometrial arteries. Tone oscillations in chorionic arteries from pre-eclamptic and growth restricted (FGR) pregnancies were reduced in amplitude whereas those in myometrial arteries had increased frequency. Inhibition of NOS further reduced oscillation amplitude in chorionic arteries from FGR pregnancies. The alterations may contribute to the vasculopathology of these conditions, or, may represent compensatory mechanisms to maintain a matching of materno-placental blood flow.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Adolescent; Adult; Arteries; Birth Weight; Blood Pressure; Bradykinin; Chorion; Female; Fetal Growth Retardation; Humans; Muscle Tonus; Muscle, Smooth, Vascular; Myography; Myometrium; Nitric Oxide; Nitroarginine; Placenta; Pre-Eclampsia; Pregnancy; Regional Blood Flow; Vasoconstriction; Vasodilation

We studied the effects of hydralazine, nicardipine, nitroglycerin, and fenoldopam (a dopamine D1-agonist) on isolated human umbilical arteries (HUA) from patients classified as normotensive and with pregnancy-induced hypertension (PIH). Umbilical artery rings were contracted with the thromboxane A(2) analog (U46619; 10(-8) M) and then exposed to cumulative concentrations of fenoldopam, hydralazine, nicardipine, and nitroglycerin. Second, rings were preexposed to prazosin (10(-5) M), phenoxybenzamine (10(-5) M), or none, and the constriction responses to increasing doses of fenoldopam or dopamine were recorded. Nitroglycerin, hydralazine, and nicardipine produced concentration-dependent relaxation of U46619-preconstricted HUA segments from normotensive and PIH patients. Fenoldopam and dopamine induced umbilical artery constriction in both normal and PIH rings at concentrations > or = 10(-5) M and > or = 10(-3) M, respectively. Phenoxybenzamine, but not prazosin, pretreatment irreversibly abolished fenoldopam-induced contraction. In this in vitro study, nitroglycerin was the most potent vasodilator of the HUA constricted with U46619, followed by nicardipine and hydralazine. However, fenoldopam constricted HUA rings only at supratherapeutic concentrations. No significant differences of vascular responses to fenoldopam (P = 0.3534), nitroglycerin (P = 0.7416), nicardipine (P = 0.0615), and hydralazine (P = 0.5514) between rings from normotensive or hypertensive pregnant patients were shown.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Dopamine; Dose-Response Relationship, Drug; Female; Fenoldopam; Humans; Hydralazine; In Vitro Techniques; Muscle Contraction; Nicardipine; Nitroglycerin; Potassium Chloride; Pre-Eclampsia; Pregnancy; Receptors, Adrenergic, alpha; Thromboxane A2; Umbilical Arteries; Vasoconstrictor Agents; Vasodilator Agents

(1) To investigate a possible association between myometrial and placental artery vasoreactivity and perfusion at the basal and chorionic plates, respectively. (2) To confirm that myometrial arteries from women with pre-eclampsia and intrauterine growth restriction exhibit an attenuated endothelium-dependent vasodilatory response.. Women with normal pregnancy, pre-eclampsia and intrauterine growth restriction had a magnetic resonance scan to assess placental perfusion using a technique called intravoxel incoherent motion. At delivery, myometrial and chorionic plate placental arteries were assessed on a wire myograph. Vessels were pre-constricted with the thromboxane mimetic U46619 and dilated with incremental doses of bradykinin.. Pre-constricted myometrial arteries from women with pre-eclampsia or intrauterine growth restriction exhibited an attenuated vasodilatory response to bradykinin, compared with normal pregnancy (P < 0.0001). Pre-constricted placental arteries exhibited a minimal vasodilatory response in all three groups of women (P = 0.10). Maximal constrictor and vasodilatory responses of myometrial arteries were not associated with the perfusing fraction at the basal plate. Maximal constrictor and vasodilatory responses of chorionic plate placental arteries were not associated with the perfusing fraction at the chorionic plate.. We confirm that myometrial arteries from women with pre-eclampsia or intrauterine growth restriction exhibit an attenuated endothelium-dependent vasodilatory response. Apart from vasoreactivity of small arteries, other factors may be involved in the control of placental perfusion.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Adult; Analysis of Variance; Arteries; Female; Fetal Growth Retardation; Humans; Myometrium; Placenta; Placental Circulation; Pre-Eclampsia; Pregnancy; Vasoconstrictor Agents; Vasodilation

Adrenomedullin is a potent vasodilatory peptide with plasma levels that increase during pregnancy. Although fetoplacental adrenomedullin levels are reported to increase in preeclampsia, maternal plasma levels may be elevated or decreased, or they may resemble those in normal pregnancy. In other hypertensive conditions, adrenomedullin increases. Therefore, we hypothesized that maternal plasma adrenomedullin levels would be higher in hypertensive pregnancies than in normotensive pregnancies and that the higher placental resistance found in preeclamptic pregnancies results from blunted activity of adrenomedullin on the vasculature. Adrenomedullin concentrations in plasma from women with normotensive pregnancies, gestational hypertension, and preeclampsia were determined by radioimmunoassay. Stem villous arteries from normotensive and preeclamptic pregnancies were dissected and mounted on a wire myograph system. Arteries were first preconstricted to 80% of their maximum constriction with U46619, a thromboxane A(2) mimetic, and exposed to cumulative doses of adrenomedullin (1x10(-)(9) to 3x10(-)(7) mol/L). Contrary to our hypothesis, there were no significant differences in maternal plasma adrenomedullin levels among patients with normal pregnancies, gestational hypertension, and preeclampsia. Adrenomedullin significantly relaxed arteries from both normal and preeclamptic placentas, but there was no significant difference between the 2 groups. During normal pregnancy, adrenomedullin may contribute to the low placental vascular resistance. This pathway appears to be intact in preeclampsia. We conclude that the increased placental vascular resistance observed in preeclampsia is due neither to reduced adrenomedullin secretion nor to an attenuated vascular responsiveness. Moreover, unlike other hypertensive disorders, there is no compensatory rise in circulating adrenomedullin levels.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Adrenomedullin; Adult; Arteries; Dose-Response Relationship, Drug; Female; Humans; In Vitro Techniques; Peptides; Placenta; Potassium Chloride; Pre-Eclampsia; Pregnancy; Vasoconstrictor Agents; Vasodilation

The effects of 8-epi-prostaglandin F(2alpha)(8-epi-PGF(2alpha)) and the thromboxane A(2)-mimetic U46619 were examined on isolated human fetal placental arteries obtained from normal pregnancies and from those complicated by pre-eclampsia. The effects of these agents were examined on both conduit and resistance arteries. 8-epi-PGF(2alpha)was found to be markedly less potent than U46619 in constricting both size vessels. Vasoconstrictor EC(50)s for 8-epi PGF(2alpha)were 4.10x10(-7) m (2.02-8.35x10(-7) m) (mean, 95 per cent CI and 2.05x10(-6) m (0.43-9.89 x10(-6) m) in conduit and resistance arteries, respectively. The maximum vasoconstriction produced by 8-epi-PGF(2alpha)(112+/-17 per cent), (relative to maximum KCl induced vasoconstriction) in conduit vessels was significantly less than that caused by U46619 (152+/-20 per cent). In resistance vessels the maximum vasoconstrictor effects to 8-epi-PGF(2alpha)(208+/-10 per cent) and U46619 (201+/-19 per cent) were similar, and in both cases significantly greater than the maximal effects seen in conduit vessels. U46619 displayed a similar vasoconstrictor potency in both conduit (EC(50)=1.21x10(-9) m, 0.58-2.51x10(-9) m) and resistance arteries [EC(50)=5.95x10(-9) m, (0.81-43.60x10(-9) m] as was found for 8-epi PGF(2alpha). 8-epi-PGF(2alpha)was equipotent in resistance arteries obtained from women with severely pre-eclamptic pregnancies (EC(50)=1.25x10(-6) m, 0.25-6.17x10(-6) m) compared with normotensive controls. However, the maximum vasoconstrictor effect induced by 8-epi-PGF(2alpha)in placental resistance arteries was significantly reduced (99+/-20 per cent) in vessels obtained from severely pre-eclamptic compared with normal pregnancies. These results indicate that 8-epi-PGF(2alpha)displays differential vasoconstrictor activity in the fetal-placental vasculature. Furthermore the vasoconstrictor effects of 8-epi-PGF(2alpha)are reduced in pre-eclampsia, the effect being selective to placental resistance vessels. This reduction may occur as a result of more serious disturbances in the placental microcirculation with the disease process in pre-eclampsia.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Adolescent; Adult; Arteries; Dinoprost; Female; Humans; Male; Placenta; Potassium Chloride; Pre-Eclampsia; Pregnancy; Receptors, Thromboxane; Vascular Resistance; Vasoconstrictor Agents

These experiments were performed to study the influence of endothelial factors on the contractile effect of the thromboxane A(2) analog U46619 and on the relaxant action of 17beta-estradiol on isolated human omental arteries from nonpregnant women, women with normal pregnancies, and women with preeclampsia.. Arterial rings (3 mm) with or without endothelium were suspended in organ chambers filled with Krebs buffer, 37 degrees C, aerated with 5% carbon dioxide in air, pH approximately 7.4, for isometric tension recording. Rings were incubated with indomethacin, N(omega)-nitro-L -arginine, or 17beta-estradiol, alone or in combination. The concentration that produced 50% of maximal effect, the area under the curve, and the maximal effect of U46619, normalized with respect to a reference contraction in response to potassium chloride, were compared.. Neither indomethacin nor N(omega)-nitro-L -arginine changed the basal tone of omental artery rings. Neither N(omega)-nitro-L -arginine nor removal of the endothelium affected either the contractile action of U46619 or the relaxant action of 17beta-estradiol. In contrast, indomethacin potentiated the contractile effect of U46619 and abolished the inhibitory effect of 17beta-estradiol in rings from all three groups. The effects of U46619 and 17beta-estradiol were significantly less in rings from women with normal pregnancy than in those from women with preeclampsia. Tissues from women with preeclampsia demonstrated the highest contractile response to U46619.. The inhibitory effect of 17beta-estradiol is not due to increased production of endothelial nitric oxide but rather involves inhibitory products of the cyclooxygenase pathway. The effect of indomethacin may result from inhibited production or release of eicosanoids or from sensitization of thromboxane A(2) receptors.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Adult; Arteries; Cyclooxygenase Inhibitors; Drug Synergism; Endothelium, Vascular; Enzyme Inhibitors; Estradiol; Female; Humans; Indomethacin; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase; Omentum; Organ Culture Techniques; Pre-Eclampsia; Pregnancy; Vasoconstrictor Agents; Vasodilator Agents

Oxidative stress may increase production of superoxide and nitric oxide, leading to formation of prooxidant peroxynitrite to cause vascular dysfunction. Having found nitrotyrosine residues, a marker of peroxynitrite action, in placental vessels of preeclamptic and diabetic pregnancies, we determined whether vasoreactivity is altered in these placentas and treatment with peroxynitrite produces vascular dysfunction. The responses of diabetic, preeclamptic, and normal placentas to increasing concentrations of the vasoconstrictors U-46619 (10(-9)-10(-7) M) and ANG II (10(-9)-10(-7) M) and the vasodilators glyceryl trinitrate (10(-9)-10(-7) M) and prostacyclin (PGI(2); 10(-8)-10(-6) M) were compared as were responses to these agents in normal placentas before and after treatment with 3.16 x 10(-4) M peroxynitrite for 30 min. Responses to both vasoconstrictors and vasodilators were significantly attenuated in diabetic and preeclamptic placentas compared with controls. Similarly, responses to U-46619, nitroglycerin, and PGI(2), but not ANG II, were significantly attenuated following peroxynitrite treatment. The presence of nitrotyrosine residues confirmed peroxynitrite interaction with placental vessels. Overall, our data suggest that peroxynitrite formation is capable of attenuating vascular responses in the human placenta.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Adult; Angiotensin II; Antihypertensive Agents; Diabetes Mellitus, Type 1; Epoprostenol; Female; Fetus; Humans; In Vitro Techniques; Muscle, Smooth, Vascular; Nitrates; Nitric Oxide; Nitroglycerin; Oxidative Stress; Placenta; Pre-Eclampsia; Pregnancy; Reactive Oxygen Species; Tyrosine; Vasoconstriction; Vasoconstrictor Agents; Vasodilator Agents

Our purpose was to compare the responsiveness of omental resistance arteries from nonpregnant women and from normotensive and preeclamptic pregnant women to selected contractile agonists.. Omental artery rings with intact endothelium from normotensive premenopausal nonpregnant women and from normal and preeclamptic pregnant women were mounted in Krebs-bicarbonate solution in organ baths for isometric tension recording. After the presence of endothelium was confirmed, cumulative concentrations of norepinephrine, serotonin, U46619, and endothelin-1 were added. Concentration-response curves were constructed and expressed as percentage of a reference 60 mmol/L potassium chloride contraction. Data analysis was by repeated-measures analysis of variance. Newman-Keuls test, and paired or unpaired Student t test, as appropriate. Statistical significance was by two-tailed p<0.05.. Endothelin-1 and U46619 increased tension similarly in all three groups. Norepinephrine increased tension in nonpregnant vessels to a greater extent than in either preeclamptic or pregnant vessels (nonpregnant 114.3 +/- 5.42% vs pregnant 65.2 +/- 10.5%, p<0.05). Nonpregnant omental artery developed significantly greater tension than did pregnant tissue at three concentrations of norepinephrine (10(-5) mol/L, 3 x 10(-5) mol/L, 10(-4) mol/L), and preeclamptic vessels developed more tension than that from normal pregnant vessels at 3 x 10(-6) mol/L (p=0.06) and 10(-5) mol/L (p<0.05). There was a negligible change in tension with increasing concentrations of serotonin in the vessels from nonpregnant women; serotonin-induced contraction in the omental arteries from normotensive pregnant women and preeclamptic patients was <6% of the potassium chloride reference contraction, but this was significantly (p<0.05) different from that of the nonpregnant women.. Omental artery segments from nonpregnant, normotensive pregnant and preeclamptic women contract similarly to endothelin-1 and U46619 but exhibit variable responses to norepinephrine and serotonin.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Adult; Arteries; Endothelins; Female; Humans; In Vitro Techniques; Isometric Contraction; Norepinephrine; Omentum; Pre-Eclampsia; Pregnancy; Premenopause; Prostaglandin Endoperoxides, Synthetic; Serotonin; Thromboxane A2; Vasoconstrictor Agents

This study on the human umbilical artery was undertaken in order to elucidate possible correlations between changes in response to vasoactive substances in vitro and abnormal umbilical artery flow velocity waveforms in vivo associated with preeclampsia and intrauterine growth retardation. The vascular reactivity to endothelin-1, noradrenalin, serotonin, the thromboxane A2 analogue U46619, substance P and prostacyclin was determined in umbilical artery segments from 13 normal pregnancies and 29 pregnancies complicated with preeclampsia and/or intrauterine growth retardation with normal or abnormal umbilical flow velocity waveforms. The contractile effect in vitro of endothelin-1 and noradrenalin was reduced in segments from pregnancies complicated by abnormal umbilical flow velocity waveforms in vivo. No differences were detected in the contractile effect of serotonin and U46619, or in the relaxatory effect of substance P and prostacyclin. In conclusion, endothelin-1- and noradrenalin-related mechanisms could be involved in the abnormal umbilical flow velocity waveforms associated with preeclampsia and intrauterine growth retardation.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Adult; Blood Flow Velocity; Dose-Response Relationship, Drug; Endothelins; Epoprostenol; Female; Fetal Growth Retardation; Hemodynamics; Humans; Muscle, Smooth, Vascular; Norepinephrine; Pre-Eclampsia; Pregnancy; Prostaglandin Endoperoxides, Synthetic; Regional Blood Flow; Serotonin; Substance P; Thromboxane A2; Ultrasonography, Doppler; Umbilical Arteries; Vasoconstriction; Vasoconstrictor Agents

Topics: 1-Methyl-3-isobutylxanthine; 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; 8,11,14-Eicosatrienoic Acid; Angina, Unstable; Angioplasty, Balloon, Coronary; Arachidonic Acid; Arachidonic Acids; Colforsin; Cyclic AMP; Cytochrome P-450 CYP2J2; Cytochrome P-450 Enzyme System; Female; Humans; Oxygenases; Platelet Activation; Pre-Eclampsia; Pregnancy; Prostaglandin Endoperoxides, Synthetic; Thrombin