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 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endothelial damage is a hallmark of acute lung injury. Endothelial mediators may increase pulmonary vascular tone and induce pulmonary arterial muscularization, thereby contributing to the pulmonary hypertension seen with acute lung injury. We measured plasma levels and net pulmonary clearance of endothelin-1, a potent endothelium-derived vasoconstrictor peptide and smooth muscle mitogen, in 26 patients with early acute lung injury, the adult respiratory distress syndrome, and pulmonary hypertension. Nineteen had another data collection at clinical improvement or worsening. Control subjects (n = 25) had no pulmonary hypertension or lung injury. Initial mixed venous and systemic arterial plasma endothelin-1 levels were elevated (4.6 +/- 0.6 SEM and 4.9 +/- 0.6 pg/ml, respectively) as compared with control subjects (0.9 +/- 0.1 and 0.6 +/- 0.1 pg/ml). The systemic arterial/venous endothelin-1 ratio was 1.1 +/- 0.1 (0.7 +/- 0.1 in control subjects), indicating a reduction in normal net pulmonary endothelin-1 clearance. With clinical improvement, as compared with clinical worsening, mean plasma endothelin-1 levels, arterial/venous ratio, and pulmonary arterial pressure fell significantly towards normal. Thus, patients with acute lung injury have marked early increases in circulating plasma endothelin-1 levels, associated with abnormal pulmonary endothelin-1 metabolism. These abnormalities reverse in patients who recover. Through its actions, endothelin-1 could contribute to the pulmonary hypertension seen in acute lung injury.
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PMID:Endothelin-1 in acute lung injury and the adult respiratory distress syndrome. 825 14

To study the potential role of endothelin-1, a potent endothelium-derived vasoconstrictor peptide, in the pathophysiology of persistent pulmonary hypertension of the newborn (PPHN), we measured arterial concentrations of immunoreactive endothelin-1 (irET-1) in 24 neonates with PPHN. Secondary diagnoses included meconium aspiration syndrome (13 patients), sepsis (2), congenital diaphragmatic hernia (1), asphyxia (1), pulmonary hemorrhage (1), aspiration of blood (1), and respiratory distress syndrome (1). Compared with irET-1 levels in umbilical cord blood in normal infants (15.1 +/- 4.1 pg/ml; mean +/- SEM) and in newborn infants with hyaline membrane disease who were supported by mechanical ventilation (11.8 +/- 1.2 pg/ml), infants with PPHN had markedly elevated circulating irET-1 levels (27.6 +/- 3.6 pg/ml; p < 0.01 vs cord blood, hyaline membrane disease). Infants with severe PPHN requiring extracorporeal membrane oxygenation (ECMO) therapy had higher irET-1 levels than infants with milder disease (31.0 +/- 4.7 for ECMO-treated infants vs 21.2 +/- 2.0 for non-ECMO-treated infants; p < 0.05). In patients treated without ECMO, irET-1 progressively decreased during the following 3 to 5 days, paralleling clinical improvement. In contrast, irET-1 concentrations remained elevated in infants with severe PPHN during ECMO therapy. We conclude that circulating irET-1 levels are elevated in newborn infants with PPHN, are positively correlated with disease severity, and decline with resolution of disease in patients who do not require ECMO therapy. Whether endothelin-1 contributes directly to the pathophysiology of PPHN or is simply a marker of disease activity remains speculative.
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PMID:Elevated immunoreactive endothelin-1 levels in newborn infants with persistent pulmonary hypertension. 815 68

Recent studies have shown that the basal release of PRL from anterior pituitary cells is inhibited by endothelin-1 (ET-1) and ET-3. To determine whether ET also regulates the synthesis and release of PRL by decidual cells, we examined the effects of ET on the synthesis and release of PRL from an enriched fraction of human decidual cells prepared by isopycnic centrifugation of enzymatically dispersed term decidual tissue. Exposure of decidual cells to ET-1 (10(-7) M) for 96 h caused a progressive decrease in basal PRL synthesis and release beginning 24 h after exposure with half-maximal inhibition occurring at an ET-1 concentration of 5 x 10(-9) M. Between 72-96 h of culture, ET-1-exposed cells synthesized 37.2 +/- 2.7% (SEM) and released 32.3 +/- 1.3% less PRL than control cells (P < 0.01). ET-1-exposed cells incubated with [35S]methionine between 72-96 h also released less [35S] PRL than control cells. Sarafotoxin S6C, an ETB receptor agonist, also inhibited basal PRL release, whereas BQ-123, an ETA receptor antagonist, had no effect on basal or on ET-1-mediated inhibition of PRL release. ET-1 also markedly inhibited the stimulation of PRL synthesis and release in response to insulin and insulin-like growth factor-1 (IGF-1). Cells exposed to insulin (100 ng/ml) and IGF-1 (50 ng/ml) alone released 61.2 +/- 3.6% and 40.0 +/- 3.8% more PRL, respectively, than control cells between 72-96 h of exposure. However, cells exposed simultaneously to insulin and ET-1 (10(-7) M) released only 17.1 +/- 3.5% more PRL than control cells during the same time period, and cells exposed simultaneously to IGF-1 and ET-1 released only 4.1 +/- 1.8% more PRL than controls during the same time interval (P vs. insulin or IGF-1 alone < 0.001 in each instance). Both basal and insulin- and IGF-1-stimulated PRL release were also inhibited by the ET isotypes ET-2 and ET-3, and by the ET-1 precursor, big ET. Since macrophages and decidual cells synthesize ET, and decidual tissue contains specific receptors for ET, the inhibitory action of ET on basal and stimulated PRL release may result from an autocrine and/or paracrine effect and appears to be mediated through the ETB receptor.
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PMID:Endothelin inhibits basal and stimulated release of prolactin by human decidual cells. 834 96

We investigated the effect of the anti-ulcer drug cetraxate on the development of the gastric ulcer induced by the submucosal injection of endothelin-1 in the rat gastric body, and its effects on gastric mucosal hemodynamics and tissue oxygenation by Laser doppler flowmetry and tissue spectrophotometry. Endothelin-1 induced gastric ulcer (ulcer length: 11.85 +/- 0.89 mm, mean +/- SEM, n = 4) which was strongly attenuated by cetraxate (ulcer length: 3.27 +/- 0.3 mm, mean +/- SEM, n = 8, p < 0.0001). Cetraxate maintained also tissue oxygenation without causing any significant effect on the endothelin-1-induced changes in gastric mucosal blood flow and volume. These results show that cetraxate exerts its cytoprotective action partly by maintaining mucosal oxygenation.
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PMID:Endothelin-1-induced gastric ulcer is attenuated by cetraxate. 835 Jun 65

Hyperinsulinemia has been implicated as a separate risk factor for the development of accelerated cardiovascular disease, but the mechanism is unknown. Recently, we and several other groups have shown that insulin stimulates the production and secretion of the vasoconstrictor peptide endothelin-1 (ET-1) from vascular endothelial cells, and hyperinsulinemia results in increased plasma ET levels in vivo. However, the interactive effects of diabetes, insulin, and glucose on ET target tissues, like those on vascular smooth muscle cells (VSMC), are not well defined. In these studies, we examined the effects of the diabetic factors on ET receptors and [3H]thymidine incorporation into cultured cells prepared from control, streptozocin-diabetic, insulin-treated diabetic, and hyperinsulinemic rats. Scatchard analysis of saturation binding studies revealed a 2-fold increase in ET receptor number in normal VSMC treated in vitro with insulin, whereas glucose had no significant effect. Neither treatment affected receptor affinity. Similarly, aortic smooth muscle cells, brain capillary pericytes, and kidney afferent arteriolar smooth muscle cells from rats made hyperinsulinemic in vivo each showed approximately a 2-fold increase in receptor number. This increase in receptor density probably resulted from the stimulation of receptor protein production, because insulin caused a maximal 2.3 +/- 0.3 (+/- SEM) fold increase in the ETA receptor mRNA expressed in cultured VSMC by 4 h. Both insulin and ET significantly increased thymidine incorporation in aortic VSMC, but ET-1 was much more potent in this regard. However, the combined effects of insulin plus ET-1 resulted in a 10-fold increase in this index of cell proliferation, significantly different from the effects of either peptide alone. We postulate that hyperinsulinemia in vivo may potentiate ET release and receptor-mediated action, thereby contributing to vascular disease in the setting of diabetes.
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PMID:Insulin stimulates endothelin binding and action on cultured vascular smooth muscle cells. 836 55

Measurements were made on 46 pairs of riveters and matched control subjects before and after a morning's work. Before starting work, the mean resting finger systolic pressure was 112 (SEM 3.3) mm Hg in the riveters, similar to 117 (1.7) in the control subjects. After cooling the middle phalanx to 10 degrees C for five minutes, 16 riveters but only one control subject exhibited digital vasospasm and these numbers were unaltered after a morning's work. A subgroup of riveters whose role was always to provide counter pressure to the rivet gun showed a higher incidence (45%) of cold induced vasospasm than did riveters who invariably held the gun (10%) or rotated between both roles (27%). Plasma levels of three markers of vascular activity, endothelin-1 (ET-1), von Willebrand factor antigen (vWFAg), and angiotensin converting enzyme (ACE), were measured in non-smoking riveters and control subjects. Before work, ET-1 concentrations were slightly lower (p < 0.05) in the riveters, but vWFAg concentration and ACE activity were similar in riveters and control subjects. Riveting for a morning did not alter ET-1 concentration or ACE activity but did induce a small increase (p < 0.05) in vWFAg concentration, which may indicate damage to the endothelium. This type of vascular assessment may be helpful in assessing vasospastic complications in workers exposed to vibration.
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PMID:An investigation into the acute vascular effects of riveting. 843 49

Urinary endothelin-1 levels were assayed from 50 gravidas with preeclampsia and 11 with normotension in the third trimester of pregnancy. Urinary endothelin-1 levels (mean +/- SEM) were similar between gravidas with normotension and preeclampsia (62.7 +/- 7.5 vs 79.8 +/- 9.3 fmol/mg urinary creatinine, respectively). Urinary endothelin-1 excretion is not significantly increased in patients with preeclampsia and therefore not a good marker for preeclampsia.
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PMID:Urinary endothelin-1: not a useful marker for preeclampsia. 843 35

In the present in vitro study we investigated the possible vasorelaxing effect of atrial natriuretic peptide (ANP) and cyclic guanosine monophosphate (cGMP) on small intramyometrial arteries precontracted by endothelin-1 (ET-1). Myometrial biopsies from normotensive pregnant women were obtained during cesarean section and arteries of resistance vessel size were dissected and mounted in a tissue chamber for isometric registration of contractile tone. In arteries preconstricted with ET-1 (10(-8)M), ANP produced a concentration-dependent relaxation of 19 +/- 5% (mean +/- SEM) and 27 +/- 7% at concentrations of 10(-7) and 3 x 10(-7) M, respectively. cGMP induced a relaxation of 13 +/- 2, 18 +/- 3, 25 +/- 4 and 30 +/- 7% at concentrations of 10(-5), 10(-4), 3 x 10(-4) and 10(-3) M, respectively. Pretreatment with ANP did not attenuate the contraction produced by ET-1. We suggest that ANP may have a vasodilating effect on preconstricted human uteroplacental vessels. It also provides evidence for the role of other endogenous or exogenous vasodilators acting via cGMP-dependent mechanisms in the counteraction of ET-1-induced contraction of the myometrial resistance vessels during pregnancy.
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PMID:Effects of atrial natriuretic peptide and cyclic guanosine monophosphate on isolated human myometrial arteries preconstricted by endothelin-1. 852 53

We investigated the vascular effects mediated by ETA and ETB receptors in human dorsal hand veins in vivo, using sarafotoxin S6c (SFTX6c) as a selective agonist of ETB receptors and endothelin-1 (ET-1) as a nonselective agonist of ETA and ETB receptors. The cyclo-oxygenase inhibitor aspirin and the nitric oxide synthase inhibitor L-NMMA were used to examine the modulating role of endothelial vasodilators on the response to SFTX6c. Drugs were all infused into the hand veins, at locally but not systemically active doses, via a 23 SWG butterfly cannula, with the exception of aspirin, which was administered orally. Hand vein size was measured by the Aellig technique. The study was performed in six healthy male subjects. Data (mean +/- SEM) were examined by ANOVA. Results are expressed as percent change from baseline at 60 min. ET-1 (5 pmol/min for 60 min) caused venoconstriction of 68 +/- 6% (p = 0.0001). SFTX6c at the same dose caused venoconstriction of 19 +/- 4% (p = 0.003). The response to SFTX6c was significantly less than to ET-1 (p = 0.002). Constriction to SFTX6c tended to increase when this agent was co-administered with aspirin (25 +/- 7%) or L-NMMA (24 +/- 10%) and was significantly potentiated when these agents were co-administered (45 +/- 4%; p = 0.01 vs. SFTX6c alone). We have demonstrated that the selective ETB agonist SFTX6c produces venoconstriction in human hand veins in vivo and that this venoconstriction is modulated by the generation of endothelium-derived vasodilators. In this vascular bed, venoconstriction rather than venodilatation appears to be the predominant effect of stimulation of ETB receptors with SFTX6c.
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PMID:Endothelium-dependent modulation of venoconstriction to sarafotoxin S6c in human veins in vivo. 858 56

By virtue of its exquisite sensitivity to the effects of endothelin-1 (ET-1), the kidney has been a consistent candidate for a pathophysiologic role for the endothelins. However, observed species differences in both receptor distribution and the subtypes mediating vasoconstriction have necessitated the development of a novel quantitative RT-PCR assay suitable for the direct investigation of human tissue, which is usually available only in very small amounts (i.e., biopsy specimens). In this study we quantified ETA and ETB receptor mRNA in normal renal cortex and medulla. For seven samples, cortex contained 0.19 +/- 0.10 amol ETA mRNA and 1.09 +/- 0.38 amol ETB mRNA/microgram total RNA (mean +/- SEM). In medulla these values were 0.47 +/- 0.25 and 2.17 +/- 1.90, respectively. The ratios of ETA to ETB were about 20:80, which correlates closely with previous studies of expressed receptor protein. This fluorescent nested quantitative RT-PCR assay provides a tool for further investigation of the human ET system at the molecular level in tissue from living individuals, and is of general applicability to the study of endogenous ligand-receptor systems.
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PMID:Comparative quantification of endothelin receptor mRNA in human kidney: new tools for direct investigation of human tissue. 858 85


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