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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The endothelium has been shown to modulate the pulmonary vascular response to hypoxia in the rat. Acute lung injury is associated with loss of hypoxic pulmonary vasoconstriction and increased pulmonary vascular permeability. Similar loss of the vascular response to hypoxia is seen after ischaemia-reperfusion injury of the myocardium. 2. The effects of reperfusion injury on pulmonary endothelial integrity, as shown by the albumin escape index and hypoxic pulmonary vasoconstriction, were investigated in isolated, blood-perfused rat lungs. 3. Ischaemia for 0.5 h, which itself caused no increase in the albumin escape index, was followed by reperfusion for 0.25 h, 0.5 h and 1 h. Controls were subjected to 2 h of perfusion only (n = 5 in all groups). The pulmonary pressor response to hypoxia (fractional inspired oxygen concentration, 3%) was measured before and after ischaemia-reperfusion, and the dilator response to acetylcholine was measured after ischaemia-reperfusion in all cases. 4. Ischaemia-reperfusion significantly increased the albumin escape index after 0.5 h (mean +/- SEM, 1.40 +/- 0.27) and 1 h (2.0 +/- 0.30) compared with controls (0.54 +/- 0.30, P < 0.05 in both cases). The pulmonary pressor response to hypoxia was augmented significantly after reperfusion when compared with baseline hypoxic pulmonary vasoconstriction (change from baseline: 13.2 +/- 4.63 and 22.2 +/- 7.1% after 0.5 and 1.0 h of reperfusion, respectively, P < 0.05). Vasorelaxation of sustained hypoxic vasoconstriction using acetylcholine was similar in both control lungs and those subjected to ischaemia-reperfusion. 5. These results suggest tht the pressor response to hypoxia is augmented after damage to the pulmonary vascular endothelium induced by ischaemic-reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pulmonary vascular reactivity and ischaemia-reperfusion injury in the rat. 814 98

Levels of calcitonin gene-related peptide (CGRP), a vasodilator peptide present in nerves and airway endocrine cells of the rat respiratory tract, are increased in hypoxic lung and decreased in plasma, suggesting impaired CGRP release. We wanted to determine whether there was an adaptive functional response to reduced CGRP levels in hypoxia. Density of binding sites for CGRP were compared with its vascular actions following hypoxia, and with binding following administration of the sensory neurotoxin capsaicin to deplete neural CGRP. Autoradiography of lung sections incubated with 125I-labelled CGRP and other vasoactive peptides was used to quantify their binding sites, in male Wistar rats exposed to periods of hypoxia (inspiratory oxygen fraction (FI,O2) = 0.1) ranging 0-10 days (n = 5 each), in controls, and in rats treated neonatally with capsaicin. Relaxation to CGRP was compared in pulmonary artery of control and hypoxic rats. CGRP binding was seen in the vascular endothelium and was significantly elevated after 5 days of hypoxia (mean +/- SEM: control 4.6 +/- 0.4 versus hypoxic 16.6 +/- 2.4 amol.mm-2). CGRP-induced (5 x 10(-7)M) relaxation of pulmonary artery was reduced, compared with controls, following 8 and 21 days of hypoxia (mean +/- SEM) percentage of relaxation to phenylephrine: 78 +/- 3, 36 +/- 5 and 32 +/- 3, respectively) and was abolished by removal of endothelium. Capsaicin treatment also significantly elevated vascular CGRP binding. Atrial natriuretic peptide (ANP) binding levels were decreased in smooth muscle of all blood vessels after 7 days of hypoxia, but endothelin-1 (ET-1) and vasoactive intestinal peptide (VIP) binding was unchanged. We conclude that the vasodilator effects of CGRP are endothelium-dependent and, whilst they are reduced in hypoxic lung, this is not due to reduction in receptors, thereby implicating alterations in the nitric oxide guanylyl cyclase system. Furthermore, adaptive responses in some peptide binding sites occur in hypoxia, which may be due to changes in endogenous peptide levels.
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PMID:Decreased endothelium-dependent pulmonary vasodilator effect of calcitonin gene-related peptide in hypoxic rats contrasts with increased binding sites. 866 97

The adhesion of activated neutrophils to endothelial cells is a key feature of the inflammatory response to cardiopulmonary bypass (CPB) because it "unlocks" a cascade of cytotoxic events. This adhesion is made possibly by the sequential involvement of two sets of neutrophil cell surface receptors: L-selection and beta 2 integrins (CD 11 a/CD 18; CD 11 b/CD 18; CD 11 c/CD 18). We have assessed the changes in the expression of these adhesion molecules in ten patients who underwent various open-heart procedures with the use of "warm" (33.4 degrees-37 degrees C) CPB. Arterial blood samples were obtained before, during and after bypass and processed for immunofluorescent flow cytometric analysis. CD 11 a expression remained unchanged throughout the study period. Conversely, CD 11 b drastically increased early after the onset of bypass (at 15 min on bypass: 172 +/- 17 [mean fluorescence (arbitrary units), mean +/- SEM] versus 63 +/- 13 before bypass. P < 0.02) and was still markedly elevated 30 min after the end of bypass (160 +/- 38, P < 0.05 versus the pre-by-pass value). CD 11 c expression underwent a similar upregulation (at 15 min of bypass: 54 +/- 5 versus 34 +/- 5 at baseline, P < 0.01). L-selectin expression did not change significantly during the period of observation. Put together, these results suggest that CPB is associated with an increased adhesive potential of neutrophils, which enhances their binding to the vascular endothelium and thereby initiates tissue damage through the release of cytotoxic mediators from adherent cells. Manipulation of integrin expression could therefore represent an effective means of alleviating the component of bypass-induced inflammatory tissue damage which is more specifically neutrophil-mediated.
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PMID:Patterns of changes in neutrophil adhesion molecules during normothermic cardiopulmonary bypass. A clinical study. 874 65

Because decidual renin may regulate uterine blood flow and decidual-endothelial cell proximity exists, we examined the modulation of decidual renin secretion by endothelial cells. Primary human decidual cell cultures were established. The effect of endothelial cells was studied by decidual-endothelial cocultures. Human umbilical endothelial cells were plated in half of the wells containing decidual cells and were then incubated for 24 h in serum-free media. The effect of endothelial cells was also studied by examining cAMP-mediated renin secretion using 10(-5) M forskolin under standardized conditions. We also examined the role of cell-to-cell contact by coculturing endothelial cells directly on decidual cultures and on cell inserts placed in decidual culture wells. The media were assayed for renin by radioimmunoassay (RIA) for angiotensin I (AI) after AI generation under standardized conditions. Statistical differences were analyzed by two-way analysis of variance (ANOVA) with randomized complete block design. Basal renin secretion, expressed as mean +/- SEM was 10.3 +/- 1.0 ng AI/ml/h. cAMP stimulation increased this to 15.5 +/- 1.3 ng AI/ml/h, P < 0.02. Coculture with vascular endothelium increased renin secretion to 24.3 +/- 2.4 ng AI/ml/h, P < 0.001. cAMP stimulation in cocultures increased renin secretion to 38.0 +/- 4.4 ng AI/ml/h, P < 0.002. There was no effect on cell growth as examined by total protein concentrations by coculturing or by cAMP. There was no increase in renin secretion when endothelial cells were cocultured using cell well inserts. Our data suggest that decidual renin secretion is increased by the presence of endothelial cells in direct contact with decidual cells. This supports a concept that in vivo-decidual-endothelial interaction may modulate decidual renin secretion and thereby influence regulation of uterine blood flow.
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PMID:Decidual renin secretion is modulated by endothelial cells. 879 69

Endothelial cells express surface adhesion molecules for leukocytes in response to myocardial ischaemia. These molecules may be released into plasma by activated cells and be detectable in soluble form. Samples were collected from the peripheral vein of 14 consecutive patients with acute myocardial infarction (AMI) at the time of admission, 6 h, and 1 and 5 days post-admission. Additionally, samples were drawn from the coronary sinus ostium and peripheral artery of seven patients undergoing coronary angioplasty (PTCA) before and after the first balloon inflation. We measured the plasma levels of soluble intercellular adhesion molecule-1 (sICAM-1) and soluble E-selectin (sELAM-1). In patients with AMI plasma levels of sICAM-1 exceeded those observed in age and sex-matched healthy subjects, (mean+/-SEM; 220.6+/-18 ng/ml) at all the time intervals assessed (358.9+/-24.5; 330.9+/-24.4; 379.4+/-39.7 and 366.8+/-47.5 ng/ml, respectively, p<0.01). sELAM-1 levels, however, were normal on admission, increased at 6 h to 52.7+/-3.8 ng/ml, p<0.05, and at day 1 (56.0+/-4.6 ng/ml) before decreasing to normal levels on the fifth day. After brief myocardial ischaemia occurring during PTCA, an increased level of sICAM-1 was observed following balloon deflation in the coronary sinus (329.2+/-20 ng/ml; p<0.05) as compared to the subjects undergoing coronary angiography, but not in the peripheral artery. sELAM-1 levels remained unchanged during angioplasty. Thus, soluble adhesion molecules expressed by activated endothelial cells are released into peripheral blood during both AMI and brief myocardial ischaemia and measurement of such molecules may prove useful for monitoring vascular endothelium activation following myocardial ischaemia/necrosis.
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PMID:The release of soluble adhesion molecules ICAM-1 and E-selectin after acute myocardial infarction and following coronary angioplasty. 931 3

1. Basal release of nitric oxide from the vascular endothelium maintains a constant vasodilating tone. Impaired nitric oxide-mediated vasodilatation has been described in hypertension and atheromatous disease. Circulatory diseases account for considerable morbidity and almost half of all deaths in people over the age of 75 years. 2. We have therefore compared nitric oxide-dependent vasorelaxation in 12 healthy elderly subjects with 12 young volunteers matched for blood pressure, cholesterol and glucose, using forearm occlusion venous plethysmography combined with brachial artery infusions of the nitric oxide synthase inhibitor, NG-monomethyl-L-arginine (L-NMMA; 1, 2 and 4 mumol/min) with noradrenaline (60, 120 and 240 pmol/min) as a control vasoconstrictor. We also measured urinary nitrate excretion after a controlled 48 h low nitrate diet as an index of total body nitric oxide production and correlated these changes with forearm blood flow responses to L-NMMA and noradrenaline in both groups. 3. The mean age and blood pressure of the elderly subjects was 76 (range 66-82) years and 132/76 (SEM 4/3) mmHg respectively, while in the young these were 27 (20-35) years and 131/72 (4/3) mmHg respectively. L-NMMA and noradrenaline produced dose-dependent reductions in forearm blood flow in both groups. L-NMMA (4 mumol/min) produced less vasoconstriction in the elderly than in the young (-37.7 +/- 2.6 versus -48.3 +/- 4.2%; P = 0.017). The mean slope of the L-NMMA dose-response curves in the elderly was significantly less than the younger group (-35.2 +/- 3.1 versus -63.7 +/- 10.6; P = 0.041). Noradrenaline, 240 pmol/min, also produced less vasoconstriction in the elderly compared with the young (-22.8 +/- 2.9 versus -35.3 +/- 5.0%; P = 0.029) although the slopes of the dose-response curves did not differ significantly. 4. Urinary nitrate adjusted for creatinine clearance was also significantly higher in the younger group (460.6 +/- 97.7 versus 205.9 +/- 64.8 mumol/day; P = 0.042) and showed a significant correlation with the percentage change in forearm blood flow in response to the maximum dose of L-NMMA (r = 0.5, P = 0.046). 5. We conclude that nitric oxide-mediated vasodilatation in the forearm vascular bed is diminished in old age and this reflects a more generalized reduction in nitric oxide production (as measured by urinary nitrate) in the circulation of older people. The blunted response to noradrenaline points to a more generalized reduction in vascular reactivity in the elderly.
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PMID:Impaired nitric oxide-mediated vasodilatation and total body nitric oxide production in healthy old age. 949 88

The mechanism behind the development of vascular complications of hypertension in the young human remains unclear. To explore the role of vascular endothelium-generated nitric oxide (a known mediator of leucocyte-platelet-endothelial interactions) in this context, we investigated markers of endothelial activation (soluble vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), P-selectin, E-selectin), and von Willebrand factor and the plasma level of the endogenous nitric oxide inhibitor asymmetric dimethyl arginine (ADMA) in a group of 31 (17 male, mean age 9.4 years) hypertensive and 9 (4 male, mean age 9.1 years) healthy, normotensive children and young adults. We found raised levels of ADMA (mean (SEM) 235 (32) n mol/l) and VCAM-1 (median (range) 1237 (675-2700) ng/ml) in the plasma of hypertensive subjects compared with those of normotensives (ADMA, 103 (7) n mol/l and VCAM-1, 1005 (425-1650) ng/ml, respectively). Furthermore, in hypertensive subjects, higher VCAM-1 concentrations (r = 0.66, p < 0.001) and vWF concentrations (r = 0.37, p = 0.04) were significantly associated with a higher plasma ADMA level. Therefore, an isolated increase in plasma VCAM-1 in hypertensives in association with raised ADMA may signify a selective "non-inflammatory" endothelial activation triggered by endothelial nitric oxide synthase inhibition. Since VCAM-1 is implicated in the origins of atherosclerosis, ADMA may be an important contributory factor in increasing the risk of atheroma formation in hypertensive children and young adults.
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PMID:Vascular endothelial cell activation associated with increased plasma asymmetric dimethyl arginine in children and young adults with hypertension: a basis for atheroma? 1085 1

The vascular endothelium has a central role in the control of microvascular tone, and it has been proposed that vascular endothelial damage occurs in septic shock, producing multiorgan failure. We have developed a method of detecting circulating endothelial cells (EC) that provides direct evidence of EC shedding in human sepsis. Human umbilical vein endothelial cells (HUVEC) were seeded in whole blood and recovered by isopycnic centrifugation to validate the technique. Blood samples were subsequently taken from 11 healthy volunteers, nine ventilated intensive care unit (ICU) control patients without sepsis, eight patients with sepsis but without shock, and 15 patients with septic shock. EC were identified by indirect immunofluorescence, using antibodies to von Willebrand factor (vWf) and the vascular endothelial growth factor receptor KDR. Mean HUVEC recovery was 86% for 20 to 100 seeded cells/ml of blood. vWf-positive EC counts per milliliter were significantly higher (analysis of variance [ANOVA], p < 0.0001) in patients with sepsis (16.1 +/- 2.7 [mean +/- SEM]) and septic shock (30.1 +/- 3.3) than in healthy (1.9 +/- 0.5) or ICU controls (2.6 +/- 0.6). KDR-positive EC counts per milliliter were also significantly higher (ANOVA, p < 0.0001) in patients with sepsis (4.2 +/- 1.1/ml) and septic shock (10.4 +/- 1.2/ml) than in healthy (0.7 +/- 0.3/ml) or ICU controls (0.5 +/- 0.2/ml). Cell counts made with anti-vWf antibody were consistently higher than those made with anti KDR antibody, but correlation between the two counts was high (r(2) = 0.93). The number of circulating KDR-positive EC was significantly higher in patients who died of septic shock than in survivors (12.0 +/- 1.6/ml versus 7.1 +/- 1.2/ml, p = 0.026). An increase in circulating EC can be identified during sepsis and septic shock. This supports the hypothesis that endothelial damage occurs in human sepsis.
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PMID:Circulating endothelial cells in patients with septic shock. 1120 46

Adhesion molecules are important in cell-cell and cell-basement membrane interactions. They are intimately involved in inflammatory reactions and a role in tumour progression has been postulated. E-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) play a role in cell adhesion to the vascular endothelium, and may have a role in tumour cell dissemination. Soluble forms of these molecules have been described and this study was established to examine these adhesion molecules in patients with breast carcinoma. Serum was obtained from 92 patients with breast carcinoma and 31 age-matched patients with benign breast disease. All samples were obtained prior to surgery. Soluble levels of E-selectin, ICAM-1, and VCAM-1 were significantly elevated in patients with Stage 4 disease compared with controls. (E-selectin 88.6 (47.9) versus 51.4 (18.4) ng/ml; P<0.001: ICAM-1 447 (249) versus 244 (79) ng/ml; P<0.001: VCAM-1 779 (159) versus 552 (135) ng/ml; P<0.001 results expressed on mean (SEM) SD placed above this.). The prognostic value of the adhesion molecules was examined. In patients with Stage 2 disease, elevated VCAM-1 was predictive of decreased survival, even when corrected for T and N status. Adhesion molecules are elevated in patients with advanced disease and elevation in VCAM-1 has prognostic significance in patients with breast carcinoma.
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PMID:Soluble adhesion molecules (E-selectin, ICAM-1 and VCAM-1) in breast carcinoma. 1244 Dec 61

Glucocorticoid (GC) excess often elicits serious adverse effects on the vascular system, such as hypertension and atherosclerosis, and effective prophylaxis for these complications is limited. We sought to reveal the mechanism underlying GC-induced vascular complications. Responses in forearm blood flow to reactive hyperemia in 20 GC-treated patients were significantly decreased to 43+/-8.9% (mean+/-SEM) from the values obtained before GC therapy (130+/-14%). An administration of vitamin C almost normalized blood flow responses. In human umbilical vein endothelial cells (HUVECs), production of hydrogen peroxide was increased up to 166.5+/-3.3% of control values by 10(-7) mol/L dexamethasone (DEX) treatment (P<0.01). Concomitant with DEX-induced hydrogen peroxide production, intracellular amounts of peroxynitrite significantly increased and those of nitric oxide (NO) decreased, respectively (P<0.01). Immunoblotting analysis using anti-nitrotyrosine antibody showed that peroxynitrite formation was increased in DEX-treated HUVECs. Using inhibitors against metabolic pathways for generation of reactive oxygen species (ROS), we identified that the major production sources of ROS by DEX treatment were mitochondrial electron transport chain, NAD(P)H oxidase, and xanthine oxidase. These findings suggest that GC excess causes overproduction of ROS and thereby perturbs NO availability in the vascular endothelium, leading to vascular complications in patients with GC excess.
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PMID:Glucocorticoid excess induces superoxide production in vascular endothelial cells and elicits vascular endothelial dysfunction. 1252 24


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