endothelin-1 and Lung-Diseases--Obstructive

The pulmonary endothelium modulates vascular tone by the release of endothelium-derived constricting (EDCF) and relaxing (EDRF) factors, among them endothelin-1, nitric oxide, prostacyclin, and putative endothelium-derived hyperpolarizing factors. Abnormalities in EDCF and EDRF generation have been demonstrated in a number of cardiopulmonary disease states, such as primary and secondary pulmonary hypertension, chronic obstructive lung disease, cardiopulmonary bypass, and congestive heart failure. An imbalance between EDCF and EDRF, termed "pulmonary endothelial dysfunction," may contribute to the alteration in vascular tone characteristic of pulmonary disease. The following review summarizes the present knowledge of the role of EDCF and EDRF in such processes with major focus on pulmonary endothelial dysfunction in hypoxia-induced pulmonary hypertension.

Topics: Animals; Antihypertensive Agents; Atrasentan; Bosentan; Controlled Clinical Trials as Topic; Disease Models, Animal; Endothelin Receptor Antagonists; Endothelin-1; Endothelins; Endothelium, Vascular; Epoprostenol; Heart Failure; Humans; Hypertension, Pulmonary; Hypoxia; Lung Diseases, Obstructive; Nitric Oxide; Oligopeptides; Peptides, Cyclic; Piperidines; Pulmonary Circulation; Pyrrolidines; Receptors, Endothelin; RNA, Messenger; Sulfonamides; Time Factors; Vasoconstriction; Vasodilation

Endothelin-1 (ET-1) has been described to have crucial effects in the initiation and evolution of pulmonary hypertension (PH) secondary to cardiac disorders. However, the precise role of ET-1 in PH induced by chronic obstructive pulmonary disease (COPD) is not yet clear. The objective of this cross-sectional study was to determine the local and peripheral plasma ET-1 profile of COPD patients with or without PH. Twenty-six COPD patients with clinical and/or laboratory findings suspicious of PH, and 20 healthy smoker volunteers constituted the study population. Patients were allocated to PH (n = 17) and non-PH (n = 9) groups according to their pulmonary artery pressures determined by right-heart catheterization. Plasma ET-1 samples, obtained from the main pulmonary artery (mixed venous blood) and peripheral blood (radial artery and brachial vein), were assessed by radioimmunoassay. Brachial vein ET-1 levels were within normal ranges in PH (2.7 +/- 0.5 pg/ml) and non-PH (3.2 +/- 0. 7 pg/ml) COPD patients compared with that of the controls (4.4 +/- 0. 1 pg/ml). Likewise, radial artery ET-1 levels in PH (3.3 +/- 0.7 pg/ml) and non-PH (2.9 +/- 0.8 pg/ml) groups, and in controls (3.4 +/- 1.1 pg/ml) were also comparable. The pulmonary artery ET-1 concentration of the PH group (13.6 +/- 3.7 pg/ml) was higher than that of the non-PH group (2.2 +/- 0.4 pg/ml) and that of the peripheral blood levels of controls. Elevated pulmonary artery ET-1 in the PH group was inversely correlated only with PaO2 levels. These results could be taken as an evidence of a local role of ET-1 in COPD-induced PH, but it remains to be clarified whether ET-1 is a marker or a mediator of PH in COPD.

Topics: Adult; Aged; Biomarkers; Blood Gas Analysis; Cross-Sectional Studies; Endothelin-1; Female; Hemodynamics; Humans; Hypertension, Pulmonary; Lung Diseases, Obstructive; Male; Middle Aged; Multivariate Analysis; Respiratory Function Tests; Sensitivity and Specificity; Statistics, Nonparametric

The present study aimed to elucidate the pathophysiological roles of endothelin (ET)-1 in patients with pulmonary hypertension and pulmonary vascular obstructive disease secondary to congenital heart disease and compare the plasma levels of ET-1 between children with and without Down syndrome.. Subjects comprised 32 children with congenital heart disease aged 0.5-14 months. Patients were classified into two groups: those with Down syndrome (Group D, n = 16); and those with nonDown syndrome (Group ND, n = 16). Heparinized blood samples were taken from a radial arterial line and plasma ET-1 levels were measured preoperatively, during cardiopulmonary bypass (CPB), a few minutes after termination of CPB, and 2, 6 and 24 h after discontinuation of CPB.. Plasma ET-1 levels were significantly higher in Group D than in Group ND at all times except for a few minutes after termination of CPB. In both groups, peak ET-1 values were obtained at 6 h after CPB. At 24 h after CPB, ET-1 concentrations returned to baseline levels before CPB in Group ND, but not in Group D. A correlation was identified between preoperative pulmonary to systemic pressure ratio and ET-1 concentration before and after CPB in both groups.. Pre- and postoperative plasma ET-1 concentrations reflect pre- and postoperative pulmonary artery conditions in both groups. Specific features in Down syndrome could be associated with ET injury and might cause persistent increases in ET concentration and prolong artificial respiration.

Topics: Cardiac Catheterization; Cardiopulmonary Bypass; Down Syndrome; Endothelin-1; Female; Heart Defects, Congenital; Humans; Hypertension, Pulmonary; Infant; Infant, Newborn; Linear Models; Lung Diseases, Obstructive; Male; Monitoring, Intraoperative; Time Factors

The purpose of this study was to evaluate the role of endothelin-1 (ET-1) and its receptors in the airway hyperreactivity of horses with obstructive pulmonary disease associated with summer pasture (SPAOPD). The right diaphragmatic lobe of the lung of 8 clinically healthy (unaffected) and 8 SPAOPD-affected horses was collected immediately after euthanasia. Bronchial rings (4 mm wide) were prepared and mounted in organ baths and attached to force transducers interfaced with a polygraph. Four rings were used to study each ET-1 receptor; 1 ring served as the control, and the other 3 were incubated with 10(-9), 10(-7), or 10(-5) M of either BQ-123, an ET(A)-receptor antagonist, or IRL-1038, an ET(B)-receptor antagonist. Cumulative concentrations (10(-8.5) to 10(-6) M) of ET-1 were applied to all rings. Using pooled pulmonary tissue from different regions of the lung, we performed a reverse-transcription polymerase chain reaction (RT-PCR) to determine ET(B)-receptor gene expression. Although ET-1 caused concentration-dependent bronchial ring contraction in both groups of horses, the rings of SPAOPD-affected horses had significantly greater contraction than the rings of unaffected horses. Whereas ET(A)-receptor blockade significantly increased the response to ET-1 in unaffected horses, ET(B)-receptor blockade significantly decreased the response in affected horses. The pA2 values showed a nonsignificant decrease in ET(A)-receptor affinity and a significant increase in ET(B)-receptor affinity in affected horses compared with unaffected horses. The ET(B)-receptor mRNA expression of the pooled pulmonary tissue showed a nonsignificant increase in affected horses compared with unaffected horses. The airway hyperreactivity to ET-1 observed in the bronchial rings from the affected horses appears to be due in part to activation of pulmonary ET(B) receptors, which appear to be inactive in unaffected horses.

Topics: Animals; Bronchial Hyperreactivity; Dose-Response Relationship, Drug; Endothelin-1; Gene Expression; Horse Diseases; Horses; Lung Diseases, Obstructive; Organ Culture Techniques; Poaceae; Receptors, Endothelin; Reverse Transcriptase Polymerase Chain Reaction; Seasons

Endothelin (ET)-l is a bronchoconstrictor peptide produced in the airways. It has been implicated in the pathogenesis of asthma and virally mediated airway inflammation and may play a role in exacerbations of chronic obstructive pulmonary disease (COPD).. Seventy one patients with COPD were followed prospectively and sampled for plasma and sputum ET-1 levels when stable and during an exacerbation. Sputum was also examined for cytokines, human rhinovirus, and Chlamydia pneumoniae.. Plasma ET-1 levels were available for 67 patients with stable COPD (mean (SD) 0.58 (0.31) pg/ml); 28 pairs of stable-exacerbation plasma samples had a mean stable ET-1 level of 0.54 (0.30) pg/ml rising to 0.67 (0.35) pg/ml at exacerbation (mean difference 0.13, 95% confidence interval (CI) 0.04 to 0.21, p = 0.004). Plasma ET-1 levels in the 67 patients with stable COPD were inversely correlated with baseline forced expiratory volume in one second (FEV(1); r = -0. 29, p = 0.022) and forced vital capacity (FVC; r = -0.38, p = 0.002). The change in plasma ET-1 levels during an exacerbation correlated with the change in oxygen saturation (SaO(2); r = -0.41, p = 0.036). In 14 stable-exacerbation pairs of sputum samples median stable ET-1 levels were 5.37 (0.97-21.95) pg/ml rising to 34.68 (13.77-51.95) pg/ml during an exacerbation (mean difference 25.14, 95% CI 3.77 to 46.51, p = 0.028). This increase in sputum ET-1 levels correlated with the increase in plasma ET-1 levels (r = 0.917, p = 0.001) and sputum interleukin (IL)-6 levels (r = 0.718, p = 0.013).. Sputum levels of ET-1 rise in COPD patients during an exacerbation and this is reflected by a smaller rise in plasma ET-1 levels. ET-1 may have a role in mediating airway inflammatory changes during exacerbations of COPD.

Topics: Aged; Biomarkers; Chlamydophila pneumoniae; Confidence Intervals; Cytokines; Endothelin-1; Forced Expiratory Volume; Humans; Lung Diseases, Obstructive; Prospective Studies; Rhinovirus; Sputum; Vital Capacity

Topics: Endothelin-1; Humans; Hypoxia; Lung Diseases, Obstructive; Oxyhemoglobins; Sleep

Nonapneic, oxyhemoglobin desaturation associated with sleep has been described in patients with chronic obstructive pulmonary disease (COPD). Hypoxemia stimulates endothelin-1 (ET-1) secretion. Once released, ET-1 can act locally to elicit sustained pulmonary artery vasoconstriction, bronchoconstriction and activation of alveolar macrophages.. The aim of this study was to examine a possible correlation between ET-1 levels and nocturnal, nonapneic, oxyhemoglobin desaturation during sleep, in patients with COPD.. We examined 48 COPD patients with formal polysomnography (EEG, ECG, airflow, respiratory muscle movement, oximeter) to detect the presence of nocturnal, nonapneic, oxyhemoglobin desaturation. Twelve of them were disqualified because of inadequate sleep or sleep apnea syndrome. Nineteen of them desaturated below a baseline sleep saturation of 90% for 5 min or more, reaching a nadir saturation of at least 85%. We collected arterial samples to measure ET-1 levels, after 5 min of the first period of desaturation, in each of the 19 patients. We also collected arterial samples in the morning, before the study, to measure baseline ET-1 levels in all patients.. Baseline arterial ET-1 levels during the day were very significantly higher in 'desaturator' COPD patients (2.058 +/- 0.252 pg/ml) compared to 'non-desaturator' COPD patients (1.382 +/- 0.159 pg/ml; p < 0.001). Also in 'desaturator' COPD patients ET-1, levels during the night were significantly higher (4.297 +/- 1.107 pg/ml) compared to those during the day (p < or = 0.001) and a significant negative correlation was observed between ET-1 levels and degree of desaturation (p < 0.0001, r = 0.9305).. According to our study we can conclude that (1) ET-1 levels are significantly higher in 'desaturator' COPD patients both during the day and during the night, and (2) ET-1 levels correlate negatively significant with the degree of the oxyhemoglobin desaturation. These findings are consistent with the hypothesis that ET-1 plays a very important role in the pathophysiological manifestations of COPD patients.

Topics: Aged; Endothelin-1; Humans; Hypoxia; Lung Diseases, Obstructive; Middle Aged; Oxyhemoglobins; Polysomnography; Sleep

Circulating and urinary levels of endothelin (ET), an endothelium-derived vasoconstrictive and mitogenic peptide have been reported to increase in patients with chronic obstructive pulmonary disease (COPD), but the mechanisms of these abnormalities are not fully understood. Our study objectives were to evaluate pulmonary and renal ET clearance in COPD patients during an acute exacerbation. Our participants included nine consecutive patients with moderate to severe COPD without signs of right heart failure admitted for acute exacerbation and ten healthy volunteers (HV) as controls. ET was detected by radioimmunoassay in venous and arterial blood as well as in a timed urine specimen. For each subject, arterial/venous immunoreactive ET ratio (ir-ETart/ir-ETven) was evaluated as an index of its pulmonary clearance. Creatinine clearance was employed in each case to obtain a corrected renal ir-ET clearance. Glomerular filtration rate (GFR) was also assessed by dynamic(99m)Tc-diethylenetriamine pentaacetic acid renal scintigraphy in six COPD patients during acute exacerbation and at recovery. The ratio ir-ETart/ir-ETven was comparable in COPD patients (0.75+/-0.12) and in HV (0.82+/-0.09). A significant difference was found with respect to 24 h ir-ET urinary excretion between COPD patients during exacerbation as well as at recovery (respectively 142.1+/-12.8 ng/24 h and 89.0+/-15.1 ng/24 h) and HV (65.1+/-10.1 ng/24 h). ET renal clearance was higher in COPD patients than in HV (29.2+/-5.2 ml min(-1)in COPD during exacerbation; 17.5+/-3.9 ml min(-1)at recovery and 13.6+/-2.4 ml min(-1)in HV, P<0.001). GFR was 69.4+/-10.0 ml min(-1)in COPD patients during exacerbation and it significantly increased at the recovery (95.5+/-20.9 ml min(-1)P<0.001). Corrected renal clearance of the peptide was significantly correlated to GFR values during the exacerbation (r=-0.81, P<0.05). Furthermore change in renal ET production resulted associated with changes in paCO(2)(r=0.83, P<0.001) and in paO(2)(r=-0.73, P<0.05). Acute exacerbation in COPD patients causes an increase in renal ET production which is partially reversible at the recovery, in the absence of significant changes in ET-1 circulating levels. ET might contribute to the renal response to hypoxaemia and hypercapnia in COPD.

Topics: Acute Disease; Aged; Endothelin-1; Glomerular Filtration Rate; Humans; Hypercapnia; Hypoxia; Kidney; Lung Diseases, Obstructive; Male; Middle Aged

Topics: Acute Disease; Biomarkers; Endothelin-1; Humans; Lung Diseases, Obstructive; Sputum

To investigate the effects of hypoxemia, hypercapnia, and cardiovascular hormones (norepinephrine, endothelin-1, and atrial natriuretic factor) on blood pressure during acute respiratory failure.. Patients with chronic obstructive pulmonary disease and acute respiratory failure were divided into four groups of 10 patients each: hypoxemia-normocapnia, hypoxemia-hypercapnia, hypoxemia-hypocapnia, and normoxemia-hypercapnia. Plasma norepinephrine levels were determined by high-performance liquid chromatography with electrochemical detection. Plasma endothelin-1 and atrial natriuretic factor levels were radioimmunoassayed after chromatographic preextraction.. Systolic blood pressure and cardiovascular hormone levels were greater in patients with hypercapnia (whether or not they also had hypoxemia) than in those with normocapnia and hypoxemia. For example, in patients with hypercapnia and normoxemia, the mean (+/- SD) systolic blood pressure was 183+/-31 mm Hg and the mean norepinephrine level was 494+/-107 pg/mL, as compared with 150+/- 6 mm Hg and 243+/-58 pg/mL in those with normocapnia and hypoxemia (both P<0.05). Similar results were seen for endothelin-1 and atrial natriuretic factor levels, and for the comparisons of hypoxemic patients who were hypercapnic with those who were normocapnic.. These results suggest that blood carbon dioxide levels, rather than oxygen levels, are responsible for hypertension during acute respiratory failure, perhaps as a result of enhanced sympatho-adrenergic activity.

Topics: Acute Disease; Adult; Aged; Atrial Natriuretic Factor; Blood Pressure; Carbon Dioxide; Endothelin-1; Female; Heart Rate; Humans; Hypercapnia; Hypertension; Hypocapnia; Hypoxia; Lung Diseases, Obstructive; Male; Middle Aged; Norepinephrine; Oxygen; Respiratory Insufficiency; Severity of Illness Index

Endothelin-1 (ET-1) is a potent vasoconstrictor peptide produced by the vascular endothelium. The purpose of this study was to elucidate the pathophysiological role of ET-1 in patients with pulmonary hypertension secondary to chronic obstructive pulmonary disease (COPD).. We measured plasma ET-1 levels during right heart catheterization both at rest and during exercise on room air and while breathing oxygen in patients with COPD. In addition, we simultaneously measured plasma levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP).. Plasma ET-1 levels at rest were significantly higher in 21 patients with COPD than in 16 control subjects (p < 0.001). For COPD patients, there was no correlation between the plasma ET-1 level and pulmonary arterial pressure or pulmonary vascular resistance at rest. On the other hand, there was a significant negative correlation between plasma ET-1 level and mixed venous oxygen tension (r = -0. 503, p < 0.05). Also, the plasma ET-1 level was positively correlated with those of ANP (r = 0.540, p < 0.05) and BNP (r = 0. 533, p < 0.05) at baseline. Oxygen administration significantly decreased plasma ET-1 levels at rest (p < 0.05). Plasma ET-1 levels did not change significantly with exercise despite the progression of pulmonary hypertension and hypoxemia. In contrast, plasma ANP and BNP levels both increased markedly with exercise (p < 0.01).. We conclude that in patients with COPD, the plasma ET-1 level is not affected by acute progression of pulmonary hypertension and hypoxemia during exercise, and persistent hypoxemia may be associated with an increase in the plasma ET-1 level. In addition, our findings suggest that ANP and BNP may modulate the pulmonary vascular tone by interacting with ET-1 in these patients.

Topics: Aged; Atrial Natriuretic Factor; Endothelin-1; Exercise; Humans; Hypoxia; Lung Diseases, Obstructive; Male; Middle Aged; Natriuretic Peptide, Brain; Reference Values

Many patients with cystic fibrosis (CF) have airflow obstruction, with peribronchial and peribronchiolar fibrosis. Endothelin (ET)-1 is a potent bronchoconstrictor with mitogenic activity for airway smooth muscle. Do the levels of ET-1 in sputum support the putative role of ET-1 in contributing to airway remodelling with airflow obstruction in CF? The levels of ET-1 in plasma, saliva and sputum from 12 adult patients with CF not in exacerbation (spontaneous sputum), 17 normal control subjects (induced sputum) and as an additional control population, nine patients with stable chronic obstructive pulmonary disease (COPD) (seven spontaneous sputum) were measured. Total and differential sputum cell counts were performed. Median (interquartile range) sputum ET-1 level was elevated in CF (77.6 (29.0-122.8) pg x mL(-1)) compared to normal subjects (6.00 (2.8-14.8) pg x mL(-1)) and COPD (16.4 (6.8-38.2) pg x mL(-1)), and in COPD compared to normal subjects. There was a slight elevation of plasma ET-1 level in CF (5.3 (3.2-6.0) pg x mL(-1)) compared to normal subjects (3.1 (1.7-4.4) pg x mL(-1)) and COPD (3.3 (2.7-4.2) pg x mL(-1)). Sputum and saliva ET-1 levels were significantly higher than plasma levels in all groups, suggesting local production or release in the respiratory tract. Sputum differential cell counts revealed pronounced neutrophilia in CF and COPD compared to normal subjects. Sputum endothelin-1 concentrations are elevated in cystic fibrosis sputum compared to chronic obstructive pulmonary disease, and in cystic fibrosis and chronic obstructive pulmonary disease compared to normal subjects. The role of endothelin-1 in contributing to airflow obstruction through bronchoconstriction and mitogenesis in cystic fibrosis needs now to be explored.

Topics: Adolescent; Adult; Aged; Cell Count; Cystic Fibrosis; Endothelin-1; Female; Humans; Lung Diseases, Obstructive; Male; Middle Aged; Sputum

Chronic obstructive pulmonary disease (COPD) represents a major cause of loss of performance in the horse. The role of endothelin (ET), a potent bronchoconstrictive and vasoactive peptide, is currently being investigated in asthma and other obstructive respiratory diseases in man. We have previously found elevated systemic and pulmonary endothelin levels in horses during exacerbation of COPD. In the present study, our aim was to examine possible variations in ET concentrations occurring during exercise in COPD horses. We compared the effects of intense treadmill exercise on the recovery of endothelin (ET) in the bronchoalveolar lavage fluid (BALF) as well as in arterial and venous blood, in a group of 5 healthy horses and a group of 5 COPD horses studied alternately in remission and while symptomatic. We also investigated the possible correlations between ET levels and pulmonary function tests during the study. While exercise did not affect the ET levels recovered in BALF among controls, it caused a significant increase (P = 0.02) among symptomatic COPD horses. During remission, wide variations of ET levels among horses, at rest and during exercise, made any significant interpretation difficult. No correlation could be found between exercise-induced changes in ET concentrations and pulmonary function tests or changes in arterial oxygen tension with exercise. We conclude that exercise appears to affect the release of ET by the airways in COPD horses, in contrast to healthy horses. It is still unclear, however, whether these differences relate to adjustments of lung function during exercise.

Topics: Animals; Blood Gas Analysis; Bronchoalveolar Lavage Fluid; Endothelin-1; Horse Diseases; Horses; Lung Diseases, Obstructive; Physical Conditioning, Animal; Radioimmunoassay; Respiratory Function Tests; Respiratory Mechanics

The molecular mechanisms by which endothelin (ET)-1 induces pulmonary hypertension are poorly understood. We investigated the effects of ET-1 on outward K+ currents of normoxic and chronically hypoxic human pulmonary arterial (PA) smooth muscle cells (HPSMCs). In normoxic HPSMCs, ET-1 has dual effects. In intact cells, 5 nM ET-1 activates the large-conductance and Ca2+-activated K+ (KCa)-channel current [IK(Ca)] by increasing intracellular Ca2+ concentration, whereas it directly inhibits IK(Ca) in isolated membrane patches. At a higher concentration (10 nM), ET-1-induced IK(Ca) inhibition predominates. In hypoxic HPSMCs, ET-1 at 5 nM significantly reduces IK(Ca). The ETA-receptor antagonist BQ-123 reverses the ET-1-induced decrease in IK(Ca). Chronic BQ-123 treatment also prevents the hypoxia-induced decrease in IK(Ca). In PA rings obtained from human organ donors, ET-1 causes a concentration-dependent increase in tension. The ET-1-mediated increase in tension is reversed by a KCa-channel agonist. The increase in tension at the highest concentration studied (9 nM) was more pronounced in PA rings obtained from patients with chronic obstructive pulmonary disease. These results imply that an ET-1-induced decrease in IK(Ca) contributes to chronic hypoxia-induced pulmonary hypertension.

Topics: 4-Aminopyridine; Analysis of Variance; Cell Hypoxia; Cells, Cultured; Charybdotoxin; Dehydroepiandrosterone; Dose-Response Relationship, Drug; Endothelin Receptor Antagonists; Endothelin-1; Humans; In Vitro Techniques; Kinetics; Large-Conductance Calcium-Activated Potassium Channels; Lung Diseases, Obstructive; Membrane Potentials; Muscle Contraction; Muscle, Smooth, Vascular; Patch-Clamp Techniques; Peptides, Cyclic; Potassium Channels; Potassium Channels, Calcium-Activated; Pulmonary Artery; Receptor, Endothelin A; Thapsigargin

To study the hemodynamic and oxygen-dynamic effects and the mechanism of nitric oxide (NO) inhalation therapy in COPD-induced chronic cor pulmonale at acute exacerbation period.. Right heart catheterization was performed in 11 cases of chronic cor pulmonale. The hemodynamic parameters and plasma endothelium-I(ET-I) level were examined and recorded before and after inhalation of 40 ppm NO for 20 minutes. The plasma level of NO and lipid peroxide Ca(2+)-Mg(2+)-ATPase(calcium pump) and Na(+)-K(+)-ATPase (natrium pump) activities of RBC membrane in 30 cases of chronic cor pulmonale and 30 healthy controls were determined synchronously.. After NO therapy, the average pulmonary pressure (PAPM) and pulmonary vascular resistance index (PVRI) were lowered by 16.6% and 25.9% respectively (P < 0.05). Intrapulmonary shunt was lowered by 16.3% (P < 0.05). ET-I also lowered and showed a positive correlation with PAPM (r = 0.59, P < 0.05). The activities of calcium and natrium pump were lowered when NO level declined, showing a positive correlation with NO concentration and negative correlation with lipid peroxides.. No inhalation therapy exerted favorable hemodynamic and oxygen-dynamic effects on COPD-induced chronic cor pulmonale in its exacerbation period. Suppression of ET-I release might be one of the important factors for pulmonary vessel relaxation. Dysfunction of calcium and natrium pump activities in the acute exacerbation period of chronic cor pulmonale were closely related to NO level.

Topics: Administration, Inhalation; Aged; Bronchodilator Agents; Calcium-Transporting ATPases; Endothelin-1; Female; Humans; Lung Diseases, Obstructive; Male; Middle Aged; Nitric Oxide; Pulmonary Heart Disease; Sodium-Potassium-Exchanging ATPase

To explore the relationship between plasma endothlin-1 (ET-1), nitric oxide (NO), calcitonin gene-related peptide (CGRP) levels and hypoxic pulmonary hypertension.. Cardiac catheterization was performed in 55 cases of chronic cor pulmonale to monitor the changes of their hemodynamic indices and to determine the levels of pulmonary arterial plasma ET-1, NO and CGRP.. The plasma ET-1 level of patients with pulmonary hypertension (Group A) was significantly higher than that of patients without pulmonary hypertension (Group B) and controls. The plasma NO level of group A was significantly lower than that of Group B and controls. The plasma CGRP level of ET-1 had a significantly negative correlation with PaO2 and positive correlation with pulmonary arterial pressure. The levels of NO and CGRP had significantly positive correlation with PaO2 and negative correlation with pulmonary arterial pressure. After 60-min oxygenation with 30% oxygen inhalation, the level of ET-1 decreased remarkably, but the levels of NO and CGRP went up notably.. These results demonstrate that hypoxia affects plasma ET-1, NO, CGRP levels in patients with chronic cor pulmonale. ET-1, NO, CGRP play synergistic roles in regulation of pulmonary arterial pressure.

Topics: Adult; Aged; Calcitonin Gene-Related Peptide; Endothelin-1; Female; Hemodynamics; Humans; Hypertension, Pulmonary; Lung Diseases, Obstructive; Male; Middle Aged; Nitric Oxide; Pulmonary Heart Disease

To investigate whether the effect of smoking on airway smooth muscle cells (ASMC) is mediated by the autocrine action of endothelin-1 (ET-1).. Abbit ASMC was cultured exposed to cigarette smoke extract (CSE), we examined the mitogenic effect CSE on ASMC in vitro and whether the ETA receptor antagonist JKC-301 can inhibit this effect.. The exposure of ASMC to 10% and 30% CSE resulted in obvious cytotoxity. The viability of ASMC was decreased, the lipid peroxides (MDA) formation was increased, and the release of lactate dehydrogenase (LDH) into supernatant was enhanced. 5% CSE significantly enhanced the cultured ASMC[3H]-thymidine (3H-TdR) incorporation by 59.9% (P < 0.01) over control. The ASMC proliferative response to 5% CSE was dose-dependently inhibited by JKC-301. Moreover, 5% CSE evoked time-dependent release of endogenous ET-1 from ASMC.. These data demonstrate that 5% CSE mediates ASMC proliferation via release and autocrine mitogenic action ET-1.

Topics: Administration, Inhalation; Animals; Cell Division; Endothelin-1; Lung Diseases, Obstructive; Muscle, Smooth; Rabbits; Smoking; Trachea

To investigate whether plasma endothelin-1 (ET-1) affects the pathologic physiologic process of pulmonary hypertension (PH) secondary to chronic obstructive pulmonary disease (COPD).. Forty-six patients with COPD who underwent right float-assisted cardiac cather examination and a supine ergometer exercise test were classified into 3 groups, that is, group A with PH, group B with latent PH and group C without PH.. (1) There was a marked higher ET-1 level in femoral arterial plasma than in pulmonary arterial plasma from group A at pre-or post-exercise or group B at post-exercise. (2) Plasma ET-1 levels of A and B groups post-exercise are higher that that in group B post-exercise than that in group C. (3) ET-1 level is also higher in group B post-exercise than that in group C. (4) There was significant correlation between the ET-1 level and mPAP, PVR, PaO2 of group A at pre- and post-exercise or group B at post-exercise.. These finding suggest a role for ET-1 in regulating pulmonary circulation of PH secondary to COPD).

Topics: Aged; Blood Gas Analysis; Endothelin-1; Exercise Test; Female; Humans; Hypertension, Pulmonary; Lung Diseases, Obstructive; Male; Middle Aged; Pulmonary Circulation