endothelin-1 and Burns

To explore whether endothelin-1 and NO are involved in the instant changes in cardiac function at early stage of severe burn.. (1) Thirty-one Wistar rats were divided into sham burn A group (SA, n = 7), burn A group (BA, n = 10), non-selective endothelin A/B receptor antagonist PD142893 group (n = 7), and the selective endothelin A receptor antagonist BQ-123 group (n = 7) according to the random number table. Rats in the latter three groups were inflicted with 30% TBSA full-thickness burn. Immediately after injury, rats in PD142893 group and BQ-123 group were intravenously injected with PD142893 (0.1 mg/kg) and BQ-123 (30 nmol x kg(-1) x min(-1)) respectively. Rats in SA group were treated the same as rats in BA group except for sham injury. The cardiac function indexes of rats in BA and SA groups including left ventricular systolic pressure (LVSP) heart rate (HR) and LV + or - dp/dt max were monitored before injury and 10, 30, 60, 180 minutes post injury (PIM) using physiological signal acquisition and processing system. The respective changes in cardiac function indexes of rate in each group between PIM 10 and pre-injury in the value of percentage were calculated. (2) Another 20 Wistar rats were enrolled and divided into sham burn B group (SB, n = 4) and burn B group (BB, n = 16) according to the random number table, and they were subjected to above-mentioned injury. Heart tissues of rats in BB group were obtained at PIM 10, 30, 60, and 180 respectively (4 rats at each time point), and that in SB group were obtained immediately after injury. Endothelin-1 and NO contents in heart tissues were determined with ELISA.. (1) Compared with the pre-injury value, LVSP, HR, LV +dp/dt max, LV -dp/dt max of rats in BA group decreased significantly since PIM 10 (with F value respectively 7.14, 16.40, 14.09 14.98, P < 0.05 or P < 0.01). No significant change was observed in above 4 indexes in rats of SB group between above mentioned two time points (with F value respectively 0.59, 0.51, 1.03, 1.04, P values all above 0.05). (2) In BA group, compared with the pre-injury value, LVSP decreased 27%, HR decreased 14%, LV +dp/dt max decreased 51%, LV -dp/dt max decreased 50% at PIM 10. Compared with those in BA group at PIM 10, cardiac function indexes were improved significantly in PD142893 group, with LVSP decreased 14% (F = 8.10, P < 0.01), HR increased 4% (F = 6.50, P < 0.01), LV +dp/dt max decreased 31% (F = 23.67, P < 0.05), LV -dp/dt max decreased 14% (F = 10.39, P < 0.01). In BQ-123 group, compared with the pre-injury value, HR increased 3%, LV -dp/dt max decreased 26% at PIM 10, which were obviously improved as compared with those in BA group (with F value respectively 6.50 and 10.39, P < 0.05 or P < 0.01); the percentage changes of LVSP and LV +dp/dt max in BQ-123 group were close to that in BA group (with F value respectively 8.10 and 23.67, P values both above 0.05). (3) Compared with those in SB group, myocardial tissue endothelin-1 content of rats in BB group increased significantly at PIM 10, 60, 180 (F = 2.85, P < 00.05 or P < 0.01), and NO content increased significantly at PIM 60, 180 (F = 1.87, with P values all below 0.05).. Endothelin-1 may participate in the instant decline of cardiac function of rats at early stage of severe burn, and plays an important role in the instant myocardial damage after injury.

Topics: Animals; Burns; Endothelin-1; Heart; Male; Myocardium; Nitric Oxide; Rats; Rats, Wistar

The purpose of this study was to investigate the influences of scald on endothelin-1 (ET-1) expression in cerebral vessels of rats, and to further elucidate the relationship between changes of ET-1 expression and scald-induced cerebral vascular remodelling resulting in cerebral vasospasm. The ET-1 levels in the cerebral basilar arteries were estimated by radioimmunoassay. Expression of ET-1 and its mRNA were determined by Western blotting and reverse transcriptase polymerase chain reaction (RT-PCR), respectively. Changes of cerebral basilar artery histology were observed and diameters were measured by angiography. The results showed that the ET-1 levels at 3h after scald were enhanced, peaking at 12h; the expression of ET-1 mRNA was also enhanced, peaking at 6h. Simultaneous vascular remodelling was observed in the cerebral basilar arteries, vasoconstriction peaking at 12h. It is suggested that ET-1 plays an important role in the pathogenesis of scald-induced cerebral vasospasm and cerebral circulation disorder.

Topics: Animals; Basilar Artery; Blotting, Western; Burns; Cerebrovascular Circulation; Endothelin-1; Random Allocation; Rats; Rats, Wistar; Vasospasm, Intracranial

To study the influence of neutrophils from severe burn patient on the morphology and function of vascular endothelial cells (VEC), and the protective effect of Shenmai concoction on VEC.. Neutrophils were isolated from the venous blood of healthy volunteers and burn patients [at 6, 24, 48 post burn hour (PBH)], and they were cocultured with VECs (ECV304) in vitro. The viability of VECs was assessed by MTT. The contents of endothelin (ET) land nitric oxide (NO) in supernatant were determined by radioimmunoassay, the ratio between ET-1 and NO (ET-1/NO) was also calculated. Blood samples from burn patients were collected at 24 PBH to repeat experiment as above, but 100 L microL isotonic saline or 100 microL Shenmai concoction in concentrations of 0.5, 2.0, 8.0 g/L was added to the cultures respectively. The effect of Shenmai concoction on above indices and morphology of ECV3O4 were also observed.. Compared with neutrophils from healthy volunteers, the activity of VECs cocultured with neutrophils from burn patients at 6 PBH was obviously decreased, the content of ET-1 obviously increased, especially with neutrophils obtained at 24 PBH (P < 0.01). The content of NO in supernatant of VEC co-cultured with neutrophils from burn patients at 6 PBH was increased obviously (48.9 +/- 2.6 micromol/L, P < 0.01). There were no obvious difference in the content of NO under the stimulation of neutrophils between that of healthy volunteers and burn patients blood obtained at 24, 48 PBH (P > 0.05). With different concentrations of Shenmai, the activity of VECs and the content of NO were obviously increased , while the content of ET-1 was significantly decreased. The morphology of VECs after treatment of neutrophils of 24 PBH and 2.0 g/L Shenmai was similar to normal VECs.. The morphology, activity of VEC, and ET/NO can be affected by neutrophils after severe burn, especially that of 24 PBH in vitro. Shenmai concoction can ameliorate above indices, thus might possibly exert protective effects on VECs after severe burn.

Topics: Adult; Aged; Burns; Case-Control Studies; Coculture Techniques; Drug Combinations; Drugs, Chinese Herbal; Endothelial Cells; Endothelin-1; Female; Humans; Male; Middle Aged; Neutrophils; Nitric Oxide; Phytotherapy

Large burns cause systemic inflammation and myocardial depression. We hypothesized that small burns affect cardiac tolerance to ischemia, and that tumor necrosis factor alpha (TNFalpha) signaling through endothelin-1 (ET) and nuclear factor kappa B (NF kappaB) are associated.. Mice were randomly assigned to four groups: burn (caused by boiling water on <2% of the body surface area), sham, burn+etanercept (TNFalpha blocker) treatment and sham+etanercept treatment. Twenty-four hours later, hearts were isolated and subjected to global ischemia followed by reperfusion. Additional hearts and burned skin lesions were sampled to evaluate expression of TNFalpha (immunoblotting) and endothelin-1 (radioimmunoassay). A NF kappaB-luciferase reporter mouse was used to evaluate NF kappaB activation.. Baseline cardiac function before ischemia (BI) was only negligibly influenced by burn or etanercept, but was reduced by burn+etanercept. Burn markedly impaired post-ischemic left ventricular function and increased infarct size in comparison with sham-treated mice. Cardiac, but nut cutaneous, expression of TNFalpha was increased in burned mice, while cardiac NF kappaB and endothelin-1 were not influenced. TNFalpha blockade reduced the detrimental effects of burn on cardiac tolerance to ischemia.. Small cutaneous burns, that did not influence baseline heart function, impaired the tolerance to ischemia. This effect may be mediated through TNFalpha, but does not involve signaling through NF kappaB or endothelin-1.

Topics: Animals; Blood Pressure; Burns; Cell Communication; Coronary Circulation; Endothelin-1; Immunoblotting; Male; Mice; Mice, Inbred C57BL; Myocardial Ischemia; NF-kappa B; Random Allocation; Skin; Tumor Necrosis Factor-alpha

To explore changes in endothelin-1 (ET-1) and calcitonin gene-related peptide (CGRP) in the myocardium after severe burn and delayed fluid resuscitation in rats at different altitudes.. Two hundred and forty male Wistar rats were employed as the experimental models with full-thickness burn of 30% total body surface area (TBSA), and they were randomly divided into three groups: delayed fluid resuscitation group (DFR), immediate fluid resuscitation group (IFR) and control group (CG). Samples of myocardial tissue were harvested at 1 hour, 6 hours, 12 hours, 24 hours, 72 hours, 168 hours postburn respectively. The changes in ET-1 and CGRP contents were determined by means of radio immunological assay.. (1)The contents of ET-1 and CGRP in DFR group tended to increase at 6 hours after burn, ET-1 was higher 2.8, 3.6 fold, while CGRP higher by 2.2, 1.5 fold (P<0.01), compared with that of CG respectively at 1517 m and 3840 m. The tendency of rise of ET-1 and CGRP was significantly less conspicuous in IFR group than that in DFR group. (2)The contents of ET-1 in DFR group tended to increase at 6 hours and reached the peak at 24 hours after burn at 1517 m, while the levels reached the peak at 72 hours after burn at 3840 m, and the change lasted for 168 hours in DFR group. The contents of CGRP increased significantly at 6 hours and reached the peak at 12 hours at 1517 m, while they reached the peak at 72 hours after burn at 3840 m.. The myocardial contents of ET-1 tend to increase significantly with the elevation of altitude after severe burn in rats, but the contents of CGRP increased lagged behind. The result show that the higher the altitude is, the more the exhaustion of protective agents of the myocardium, thus resulting in changes in ET-1/CGRP.

Topics: Altitude; Animals; Burns; Calcitonin Gene-Related Peptide; Disease Models, Animal; Endothelin-1; Male; Myocardium; Random Allocation; Rats; Rats, Wistar; Resuscitation

The purpose of this study was to evaluate effects of early wound excision on changes in NO and endothelin-1 (ET-1) level in the plasma after extensive burn injury. The effects on vascular permeability and hepatic blood flow (HBF) were also assessed. Male Wistar rats were used for this study. A 30% total body surface area (TBSA) third-degree burn was made on the back. Then animals were divided into four groups. Burn group (n = 13), burn alone; infusion group (n = 13), burn injury and fluid resuscitation; early excision group (n = 13), burn injury, total wound excision at 30 min after the injury followed with immediate allogenic skin graft and fluid resuscitation; and the sham group (n = 15). The sham group and the early excision group did not show significant changes in the NO and ET-1 level in plasma during experimental period, while the burn group and the infusion group showed significant increase in the NO and ET-1. The early excision group also did not show hypovolemia, and the significant decrease in the HBF. These data suggest that the increased NO and ET-1 in plasma following thermal injury were originated from burned tissue and the removal of these injured tissue has beneficial effect on the vascular permeability and the changes in HBF.

Topics: Animals; Burns; Capillary Permeability; Endothelin-1; Fluid Therapy; Liver Circulation; Male; Nitric Oxide; Rats; Rats, Wistar; Skin Transplantation; Urination

To describe early sequential profiling of circulating levels of tumor necrosis factor alpha (TNF-alpha), TNF-1 and TNF-2 soluble receptors (sTNFR1 and sTNFR2), and of endothelin (ET-1) in patients with severe burn injury, and its association with mortality.. Prospective study.. Intensive Care Burn Unit at a community hospital.. Twenty patients with total burn surface area (TBSA)> or = 30%.. None.. Patients were enrolled within 6 h from the injury. Blood samples were drawn at zero, 6, 12, and 24 h for sequential ELISA measurement of plasma marker levels. Data are expressed as mean+/-SD. Age, TBSA, and inhalation injury were not significantly different between survivors ( n=9; 30+/-13 years, TBSA 40+/-12%) and nonsurvivors ( n=11, 38+/-15 years, TBSA 56+/-20%). sTNFR1 levels were increased in nonsurvivors (2937+/-1676 pg/ml; 4548+/-1436 pg/ml) as compared to survivors (1313+/-561 pg/ml; 2561+/-804 pg/ml) at 6 h and 24 h, respectively ( P=0.01 and 0.002). sTNFR2 levels were significantly increased in nonsurvivors (4617+/-1,876 pg/ml vs 2611+/-1,326 pg/ml) only at 6 h ( P=0.015). TNF-alpha and ET-1 levels were not different between nonsurvivors and survivors. After adjustment for TBSA, sTNFR1 and sTNFR2 remained significantly higher in nonsurvivors.. Early and progressive increase in sTNFR1 and sTNFR2 levels is associated with higher risk for poor outcome in severely burned patients.

Topics: Adolescent; Adult; Aged; Analysis of Variance; APACHE; Biomarkers; Burns; Endothelin-1; Female; Humans; Middle Aged; Prospective Studies; Receptors, Tumor Necrosis Factor; Tumor Necrosis Factor-alpha

Topics: Animals; Burns; Endothelin-1; Hypothalamus; Male; Paraventricular Hypothalamic Nucleus; Pituitary Gland; Rats; Rats, Sprague-Dawley; Supraoptic Nucleus

In order to investigate the pathophysiological role of ET-1 in paraventricular nucleus of hypothalamus (PVH) under burn, changes in synthesis and secretion of endothelin-1 (ET-1) in PVH after burn were observed by in situ hybridization and immunohistochemistry. The intensity of ET-1 mRNA and ET-1-immunoreactivity (ET-1-ir) were quantized by image analysis.. Compared with the control group (sham burn, 100% +/- 25%), no significant change in the intensity of ET-1 mRNA positive hybridization signal in PVH was found at 15 min postburn, while the intensity increased significantly both at 60 min (138% +/- 26%, P < 0.05) and at 180 min postburn (167% +/- 18%, P < 0.01). Intensity of ET-1-ir in the neurons in PVH decreased significantly at 15 min postburn to 6.3% +/- 1.5% of the control (P < 0.01) and gradually recovered to 23.1% +/- 2.9% and to 44.1% +/- 3.8% at 60 min and 180 min postburn respectively, while still significantly lower than that in control (P < 0.01).. The results demonstrated that the synthesis and secretion of ET-1 in rat PVH increased significantly after burn in rats, suggesting that ET-1 in PVH played an important pathophysiological role under burn.

Topics: Animals; Burns; Endothelin-1; Male; Neurons; Paraventricular Hypothalamic Nucleus; Rats; Rats, Sprague-Dawley; RNA, Messenger

Topics: Burns; Endothelin-1; Humans

Remote organ dysfunction during resuscitation of severe thermal injury is characterized by early, transient pulmonary insufficiency and cardiac contractile dysfunction. Thermal injury is typified by profound systemic alterations of endothelial immunological, vasoactive, and barrier functions. The unique location of this ubiquitous, fragile monolayer makes it vulnerable to circulating serum factors created at remote cutaneous wounds. We examined endothelial "activation" in 2 distinct cell types, human coronary and pulmonary endothelial cells (EC), after severe thermal injury. By using human serum isolated at specific times after thermal injury ("early" [2 h post-burn] or "late" [26 h post-burn]), the endothelial release of vasoactive mediators, ICAM-1 expression, and monolayer permeability were assessed in vitro. Early burn serum enhanced coronary EC vasoconstrictor (ET-1) release and ICAM expression, inhibited vasodilator (PGI2) release, but had no effect on permeability. Conversely, under similar conditions, pulmonary EC PGI2 release and permeability were enhanced, ET-1 release was diminished, but ICAM was unaffected. Late burn serum enhanced vasodilator (NO) release and permeability to albumin in both coronary and pulmonary EC, whereas ET-1 release was inhibited. Under these conditions, only pulmonary ICAM expression was significantly enhanced. These data suggest that human endothelium isolated from divergent vascular beds are activated by burn injury in a unique manner for time post-burn and vascular site of cell origin.

Topics: Adult; Burns; Cell Membrane Permeability; Cell Survival; Cells, Cultured; Dinoprostone; Endothelin-1; Endothelium, Vascular; Epoprostenol; Humans; Intercellular Adhesion Molecule-1; Nitric Oxide; Organ Specificity; Vasodilator Agents

This study was carried out to investigate the role of endogenous endothelins in intestinal motility following bum injury by using a nonselective endothelin-1 (ET-1) antagonist and to evaluate the ET-1-mediated reactive oxygen metabolite formation and neutrophil infiltration following burn injury. In 2 h and 3 day postburn groups, transit indices were significantly decreased as compared to corresponding sham groups. Transit index was not significantly changed by PD156252 pretreatment in the 2 h postburn group, whereas the delay in transit was abolished in the ET-antagonist treated 3 day postbum group. In the 2 h postburn group, tissue-associated myeloperoxidase (MPO) activity value was found to be increased compared to corresponding sham group, while PD156252 pretreatment partially reversed this effect. Although MPO activity levels were not significantly different between 3 day postburn and corresponding sham groups, MPO levels showed a significant increase in ET antagonist-treated group as compared to the corresponding burn group. In the early phase of the burn, there was no significant difference in protein oxidation levels among the groups. In the 3 day postburn group, protein oxidation levels in ET-antagonist-treated group showed an increase compared to its corresponding burn group. In conclusion, the results demonstrate that endogenous endothelins have an important role in the systemic response to burn injury, as observed by a delay in intestinal motility and an infiltration of neutrophils. Although the results of the animal studies are not readily applicable to burned patients, the present study may suggest that the burned patient's condition should be carefully evaluated to secure a proper and early enteral feeding.

Topics: Analysis of Variance; Animals; Burns; Disease Models, Animal; Endothelin Receptor Antagonists; Endothelin-1; Enzyme Inhibitors; Female; Follow-Up Studies; Gastrointestinal Motility; Intestine, Small; Male; Neutrophil Infiltration; Oligopeptides; Oxidation-Reduction; Peroxidase; Proteins; Rats; Rats, Wistar; Reactive Oxygen Species; Vasoconstrictor Agents

Most investigators have reported high levels of endothelin (ET)-1 in patients with thermal injury. We attempted to examine the hypothesis that ET-1 levels increase in patients with severe burn injury.. Plasma from 28 adult subjects, 14 of whom had thermal injuries with a median (range) percentage of total burn surface area of 22% (20%-76%), was assessed for ET-1 and tumor necrosis factor (TNF) alpha. Samples from closely age-matched patients were obtained on admission (day 1) and 24 hours postinjury (day 2). Samples were obtained before blood transfusion or surgical treatment occurred. Enzyme immunoassay techniques suitable for the measurements of the cytokines were used.. Median (range) of TNF-alpha was higher in patients (day 1, 10.0 ng/L [1.2-35.0 ng/L]; day 2, 12.0 ng/L [0.4-39.0 ng/L]) than controls (0. 8 ng/L [0.3-3.2 ng/L]) (P<.005) while ET-1 levels remained significantly unchanged in patients (mean [SD], day 1, 183.0 [42.2] ng/L; day 2, 204.7 [41.7] ng/L) compared with controls (170.0 [59.8] ng/L) (P>.05).. We observed no significantly raised levels of ET-1 in patients with thermal injury within 24 hours after burn injury. We found no significant correlation between the plasma levels of TNF-alpha and ET-1. Endothelin-1 levels did not seem to reflect severity of illness. The actual evaluation of ET-1 release in patients with thermal injury could enhance the pathophysiological study of human thermal injury.

Topics: Adult; Aged; Aged, 80 and over; Burns; Endothelin-1; Female; Humans; Injury Severity Score; Male; Middle Aged

Endothelin-1 (ET-1) gene transcription and endothelin-1-immunoreactivity (ET-1-ir) in the supraoptic nucleus (SON) of rat hypothalamus were respectively observed by in situ hybridization and immunohistochemistry after scald. Intensity of ET-1 mRNA and endothelin-1-immunoreactivity (ET-1-ir) was quantified by image analysis. Compared with the control (sham scald) group, no significant change in the intensity of ET-1 mRNA positive hybridization signals in SON was found 15 min post-scald, while there was a 35.1% increase in the positive hybridization signal intensity 60 min post-scald (P<0.05) and a 62.4% increase 180 min post-scald (P<0.01). The content of ET-1-ir in SON decreased significantly to 8.5% of the control 15 min post-scald (P<0.01), and gradually recovered to 31.5% and 52.4% of the control 60 min and 180 min post-scald respectively, though still significantly lower than the control (P<0.01). Pre- and post-scald ET-1 gene transcription in rat hypothalamus was also measured by Northern blot hybridization. No significant difference in the quantity of ET-1 mRNA was found between 15 min post-scald data and those of the control. The quantity increased to a significantly higher level 60 min post-scald (P<0.05) and further increased to 2.5 creased to 2.5 fold of the control 180 min post-scald (P<0.05). In addition, the Northern blot hybridization showed that the post-scald size of ET-1 mRNA remained unchanged despite of the increase in quantity. In view of the neuroendocrine role of SON, the changes in ET-1 mRNA and ET-1-ir in SON resulting from scald suggest that ET-1 may play an important role in neuroendocrine reactions following scald.

Topics: Animals; Burns; Endothelin-1; Hypothalamus; In Situ Hybridization; Male; Random Allocation; Rats; Rats, Sprague-Dawley; RNA, Messenger; Supraoptic Nucleus; Transcription, Genetic

The importance of early cardiac myocyte damage during postburn trauma has been emphasized in recent years. However, its pathogenesis, prevention, and treatment have not been fully clarified. The aim of this study is to define its pathogenesis.. Rats with 30% third-degree burns were used. Cardiac biochemical markers reflecting cardiac myocyte damage including troponin T, cardiac myosin light chain 1, creatinine kinase and its cardiac-specific isoenzyme compound, as well as inflammatory mediators such as tumor necrosis factor, endothelin/nitric oxide ratio, malondialdehyde, and superoxide dismutase, were determined.. Cardiac biochemical markers reflecting cardiac myocyte damage, including troponin T, cardiac myosin light chain 1, cardiac-specific isoenzyme compound, were all significantly elevated between 3 hours and 24 hours after burn. Changes in tumor necrosis factor, endothelin/nitric oxide ratio, and malondialdehyde were similar to those of cardiac biochemical markers. In contrast, levels of superoxide dismutase declined markedly after burn.. The findings of this study showed that considerable amounts of myocardial constructive protein degradation and release due to destruction of cardiac myocytes occurred early after severe burns. The inflammatory mediators released after burn injury may be involved in the pathogenesis of myocardial destruction.

Topics: Animals; Biomarkers; Burns; Creatine Kinase; Disease Models, Animal; Endothelin-1; Heart Diseases; Inflammation; Male; Malondialdehyde; Myocardium; Myosin-Light-Chain Kinase; Nitric Oxide; Rats; Rats, Wistar; Superoxide Dismutase; Time Factors; Troponin T; Tumor Necrosis Factor-alpha

The unique location of the endothelium makes it vulnerable to injury from circulating factors created at remote wounds. In this study, we examined the effect of a sequential burn and lipopolysaccharide (LPS) challenge on endothelial function in vitro.. Human umbilical vein endothelial cells treated with 20% human serum isolated from burn patients (>40% total burn surface area) at 2 and 24 hours postinjury. Cultures were subsequently treated with Escherichia coli LPS:0111:B4 (0.10-100ng/mL). Endothelin-1 (ET-1), 6-ketoPGF1a, and NO2/NO3 were detected by using specific enzyme immunoassays.. Burn serum did not alter endothelial ET-1, PGI2, or NO secretion compared with Control serum. LPS significantly enhanced 6-ketoPGF1a (54,242+/-14,466 pg/10(6) cells) and NO2/ NO3 (723+/-210 microM) secretion, but not ET-1 compared with Control serum alone (3,878+/-963 and 219+/-110). Burn serum pretreatment significantly enhanced the ET-1 response to LPS (303+/-36 pg/10(6) cells vs. 193+/-47). The 6-ketoPGF1a (16,509+/-3,785) and NO2/NO3 (354+/-98) responses to Burn/LPS were significantly diminished compared with Control/LPS. Although this level of 6-ketoPGF1a was elevated compared with Control alone (7,518+/-2,299), NO2/NO3 was unchanged (significance at p < 0.05).. Thermal injury may prime remote endothelium and alter the response to a septic focus with an enhanced vasoconstrictor (ET-1) and diminished vasodilator (PGI2/NO) response, a situation that may contribute to postburn distal organ injury.

Topics: Adult; Analysis of Variance; Burns; Cells, Cultured; Endothelin-1; Endothelium, Vascular; Endotoxins; Epoprostenol; Escherichia coli; Humans; Immunoenzyme Techniques; Nitric Oxide; Umbilical Veins; Vasoconstriction; Vasodilation

In the paper authors gathered hitherto existing opinions concerning endothelin, its structure, biological role and mechanisms of action. A special attention was paid to children and the activity of endothelin in physiology and pathology in various stages of development.

Topics: Adolescent; Burns; Child; Child, Preschool; Endothelin-1; Health Status; Humans; Infant; Tumor Necrosis Factor-alpha

We studied expression of messenger RNAS for endothelin-1 (ET-1) and its receptor subunits (ETA, ETB) by northern blot hybridization and in situ hybridization in rat kidney following 30% TBSA full thickness burns.. Expressions of that ET-1, ETA, and ETB mRNA expression are all evidently increased at 1 hour postburn. ET-1 and ETA reached its maximal mRNA expression at 3 hour postburn. ET-1 mRNA distributed primarily on glomerular endothelial cells and tubular epithelial cells in cortex. ETA mRNA predominantly presented on smooth muscle cells of small arterioles in renal cortex. However, the peak time of ETB mRNA expression is at 6 hour postburn and mainly localized on renal medullary tubular epithelial and collecting duct cells.. These findings suggest that 1. ET-1 acts principally as a local paracrine/autocrine peptide. 2. Increased ET-1 that activated ETA receptors accentuated expression on vascular smooth muscle cells will result in renal cortex ischemia. 3. Accentuated expression of ETB receptor on tubular epithelial cells may induce renal natriuretic action and reduction of water execretion. 4. Increased ET-1 and its receptors in kidney play an important role in the pathogenesis and development of renal function impairment following severe burn.

Topics: Animals; Burns; Endothelin-1; Gene Expression; Kidney; Rats; Rats, Wistar; Receptor, Endothelin A; Receptor, Endothelin B; Receptors, Endothelin; RNA, Messenger

To observe the changes of endothelin-1 (ET-1) concentration, immunohistochemical distribution, mRNA expression and localization in kidney of severe burn rat.. Wistar rats sustained with 30% TBSA III degree burn were divided randomly into 6 groups: normal control, 1, 3, 6, 12, and 24 postburn hour (PBH). The items studied were: the level of ET-1 in renal vein plasma and kidney tissue (cortex, outer medulla and inter medulla respectively), immunocytochemical distribution of ET-1 in kidney tissue by light and electron microscopy, mRNA expression of ET-1 in kidney by northern blot hybridization, localization and enumeration of mRNA expressiong cells of ET-1 by in situ hybridization.. The rat kidney secretion and mRNA expression of ET-1 more evidently increased at 1, 3 PBH respectively than in normal control (P < 0.01), They distributed primarily on endothelial cells, glomerular mesangial cells. Tubular epithelial cells reached maximal mRNA expression and immunoreactivity at 3, 6 PBH respectively. Immune electron microscopic study demonstrated that ET-1 (gold particles) localized on the intracellular lumen surface of endothelium but on both apical and basal surfaces of epithelium.. Secretion and mRNA expression of ET-1 increased obviously in kidney in early stage after severe burn.

Topics: Animals; Burns; Endothelin-1; Gene Expression; Kidney; Random Allocation; Rats; Rats, Wistar; RNA, Messenger

Human lung cultured vascular endothelial cells model was established in vitro. Two kinds of skin extracts (human burned skin extracts, HBSE, and human natural skin extracts, HNSE) were added to cultured endothelial cells. The results showed that HBSE exerted toxic effect on endothelial cells in vitro. There were significantly higher contents of ET-1, NO, TNF-alpha, and abnormal structural changes in EC in the HBSE group.

Topics: Burns; Cells, Cultured; Endothelin-1; Endothelium, Vascular; Humans; Lung; Nitric Oxide; Skin; Tissue Extracts; Tumor Necrosis Factor-alpha

After the dynamic observation of postburn endothelin changes in plasma on severe burn rat model, we detected ET-1 mRNA expression and cell localization in some organs such as heart, lung, liver and kidney with in situ hybridization technique. We that endothelin concentration in plasma rapidly increased postburn (it reached its climax at 6th hour and maintained fairly high level even at 24th hour postburn). Meanwhile in situ hybridization indicated that ET-1 mRNA expression intensity and number of positive cells rapidly increased postburn. The expression climaxes of which appeared decreasing in turn from kidney, liver, lung to heart and the types of positive cells increased. This may due to the endothelin's functions of contracting blood vessels and regulating the redistribution of blood flow and be helpful for guaranteeing blood perfusion of important organs under shock state, but the overexpression of ET-1 mRNA may make the ischemic and anoxic damages to organs more severe.

Topics: Animals; Burns; Endothelin-1; In Situ Hybridization; Kidney; Liver; Lung; Male; Rats; Rats, Wistar; RNA, Messenger; Viscera

Endothelin-1, a peptide isolated from vascular endothelial cells, facilitates the constriction of vascular smooth muscle and various pharmacological actions including vasodilation, the proliferation of smooth muscle cells and fibroblasts, and the stimulation of arachidonic acid metabolism. In this study, plasma, urine, and blister fluid endothelin-1 concentrations were determined in burn patients and changes in vasoactive substances derived from endothelial cells secondary to burns were investigated. Plasma endothelin-1 concentrations in burn patients were significantly lower than those in healthy individuals at rest. However, extremely high blister fluid endothelin-1 concentrations were observed within 30 hours of a burn. The amounts of endothelin-1 excreted in urine by burn patients over 24 hours also were higher than those in healthy individuals. The finding of high concentrations of endothelin-1 in blister fluids suggests that endothelin-1 is produced at wound regions in burn victims. Clinically, it appears that endothelin-1 is involved in circulation at the wound surface or in the healing of burns.

Topics: Adult; Arachidonic Acid; Blister; Burns; Endothelin-1; Fibroblasts; Humans; Middle Aged; Muscle, Smooth

Plasma concentrations of endothelin-1 (ET-1) and thrombomodulin (TM) were determined in patients with burns to examine their relation to the severity of illness. Tumor necrosis factor-alpha (TNF-alpha) was also measured, and its relationship to ET-1 and TM determined. Twenty-three burn patients were evaluated, who had a total burn surface area (TBSA) of at least 20 per cent. ET-1 was measured by radioimmunoassay (RIA). TM and TNF-alpha were measured by enzyme-linked immunosorbent assay (ELISA). Both the ET-1 and TM concentrations were significantly higher in the patients who developed sepsis than in those who did not and in the patients who eventually died than in those who survived. Maximum plasma concentrations of ET-1 and TM were significantly correlated with the acute physiological and chronic health evaluation II score. There was also a significant correlation between the plasma levels of TNF-alpha and both ET-1 and TM. ET-1 and TM closely reflect the severity of illness in patients with burns in the infectious stage; TNF-alpha may be involved in the production of ET-1 and TM.

Topics: Adult; Aged; APACHE; Body Surface Area; Burns; Endothelin-1; Enzyme-Linked Immunosorbent Assay; Female; Humans; Male; Middle Aged; Radioimmunoassay; Sepsis; Severity of Illness Index; Survival Rate; Thrombomodulin; Tumor Necrosis Factor-alpha; Wound Infection

The dynamic changes of endothelin in sera of early burnt rats and the effects of endothelin-1 on the permeability of vascular endothelial cells were investigated. In the early phase of 30% (II degree) total body surface area (TBSA) burn rat model, we measured the concentration of endothelins in plasma, the water contents in main organs and the permeability of endothelial monolayer cultured on micropore membrane to Hank's solution or 5 g/L albumin Hank's solution. Endothelin concentration in burnt rat sera was firstly increased dramatically, showing a peak at 6 hours postburn, and then remained significantly higher than the basic level (P < 0.01). The changes of endothelin were correlated with the alteration in water contents in main organs after burn. Moreover, if the cultured endothelial cells were exposed to 0, 1, 10, 100 nmol/L endothelin 1 for 60 min, it was found that the filtration volume (Jv) and the filtration coefficient (Kf) of endothelial monolayer were significantly enhanced as determined by either Hank's or albumin (5 g/L) perfusion, while the osmotic reflection coefficient (sigma) (to protein) decreased in a dose-dependent pattern. The present results suggest that the postburn elevated endothelin may not only mediate the blood flow distribution via potent vasoconstriction, but also directly increase the vascular permeability. The mechanism(s) of the latter event needs to be further clarified.

Topics: Animals; Burns; Capillary Permeability; Cattle; Cells, Cultured; Endothelin-1; Endothelium, Vascular; Male; Pulmonary Artery; Rats; Rats, Wistar