Biomedical subjects

H P Kuo

Publications and source records attributed to H P Kuo.

At least 19 recordsLinked to original sources

PubMed1996

Effect of beta 2-adrenoceptor agonists on plasma potassium and cardiopulmonary responses on exercise in patients with chronic obstructive pulmonary disease.

OBJECTIVE: The effect of beta 2-adrenoceptor agonist-induced hypokalaemia on cardiac arrhythmias might be exacerbated during exercise, especially in patients with more compromised airway function. METHODS: To evaluate the effect of beta 2-adrenoceptor agonists on plasma potassium and cardiopulmonary function during exercise, two identical submaximal treadmill exercise tests were performed, at least 48 h apart, by 13 patients with moderate to severe COPD (11 men and 2 women, mean age 66 y, mean FEV1/FVC ratio 48.9 (2.8)% 30 min after they had received nebulised fenoterol or salbutamol (2 mg). The experiment was done as a randomised, double-blind, crossover trial after an initial baseline study with vehicle (0.45% saline). Plasma potassium concentration, spirometry and the degree of breathlessness (Borg scale) were measured before treatment and immediately after exercise; oxygen saturation, QTc interval and cardiac rhythm were monitored continuously before, during and for 30 min after exercise. RESULTS: After the saline control, exercise caused an increase in Borg rating (of 4.9), a premature ventricular contractions (VPC) (2.8 beats/min), and a fall in oxygen saturation (-6.7%), but no significant change in plasma potassium (+0.04 mEq.dl-1), FEV1 or QTc interval. Inhalation of fenoterol and salbutamol did not affect QTc interval, Borg scale or VPC frequency at rest, but significantly increased the duration of exercise undertaken to reach the submaximal levels (786 s, versus 783 s) compared to the vehicle control. Following exercise, plasma potassium fell after fenoterol by 0.2 mEq.dl-1 and it increased after salbutamol by 0.1 mEq.dl-1 compared to baseline levels. Plasma potassium after exercise was significantly lower after fenoterol (3.2 mEq.dl-1) compared to the saline control (3.7 mEq.dl-1) and salbutamol (3.6 mEq.dl-1). Neither fenoterol nor salbutamol had any significant effect on the change in FEV1, oxygen saturation, Borg scale, frequency of VPCs or QTc interval during or after exercise compared to the saline control. CONCLUSION: When compared to salbutamol 2 mg, fenoterol 2 mg caused more marked hypokalaemia but no significant difference in cardiopulmonary response in patients with COPD during exercise.

Adrenergic beta-Agonists↗

PubMed1996

Pulmonary actinomycosis appearing as a "ball-in-hole" on chest radiography and bronchoscopy.

A 40 year old diabetic man with pulmonary actinomycosis was admitted to hospital with recurrent haemoptysis. The chest radiograph showed an air meniscus in the left upper lobe, a rare presentation of pulmonary actinomycosis. Bronchoscopic examination revealed a mass in a cavity which has never been reported previously. He underwent lobectomy and the surgical specimen revealed sulphur granules, the typical pathological finding of actinomycosis, without evidence of fungal or mycobacterial infection.

Actinomycosis↗

PubMed1996

Differential effects of nasal continuous positive airway pressure on reversible or fixed upper and lower airway obstruction.

Our study was to assess whether there were differential effects of nasal continuous positive airway pressure (nCPAP) on different kinds of obstruction in either upper or lower airways in patients with chronic obstructive pulmonary disease (COPD). nCPAP (6 cmH2O for ten minutes) was applied to 7 patients with reversible extrathoracic upper airway obstruction (RUAO) and 3 patients with fixed extrathoracic upper airway obstruction (FUAO). Eighteen stable asthmatics, receiving methacholine challenge to induce a more than 20% reduction in FEV1, were randomly investigated for the effect of nCPAP or sham pressure on reversible lower airway obstruction. Nine stable COPD patients were enrolled to study the effect on irreversible lower airway obstruction. Maximal expiratory and inspiratory flow volume curves and dyspnoea scores were obtained before and after immediate withdrawal of nCPAP. In the RUAO group, nCPAP significantly improved stridor and dyspnoea scores, decreased the ratio of FEF50/FIF50 from 2.05 +/- 0.25 to 1.42 +/- 0.16, and increased peak inspiratory flow (PIF) as well as forced inspiratory vital capacity by 26 +/- 8% and 9 +/- 4%, respectively. In expiratory phase, there was no significant change in pulmonary functions. In asthmatics, nCPAP significantly reversed methacholine-induced bronchoconstriction increasing forced vital capacity by 10 +/- 3%, FEV1 by 15 +/- 4% and PIF by 32 +/- 11%. nCPAP significantly increased the response to bronchodilators. The improvement in airflow rate persisted for at least 5 min after nCPAP withdrawal and was highly correlated with the response to bronchodilators. There was no significant effect of nCPAP on airflow rate in COPD patients. Subjective dyspnoea score changes paralleled the pulmonary function improvement. We conclude that there are differential effects of nCPAP on airflow rates in patients with different nature of airway obstruction. Patients with airway obstruction caused by structural changes may not benefit from the use of nCPAP in improving airflow rates.

Adolescent↗

PubMed1996

Effect of nebulized fenoterol on spirometry, dyspnea sensation changes during exercise in patients with chronic obstructive pulmonary disease.

Airflow limitation impairs exercise capacity in patients with chronic obstructive pulmonary disease (COPD). Bronchodilators have been shown to increase exercise tolerance in patients with COPD by mechanisms yet unclarified. We studied the effect of nebulized fenoterol (0.5 mg/ml) on the 6-minute walking test (WT) 60 mins after a control WT using a nebulized saline control in 16 patients with moderate to severe COPD. Before and immediately after each WT, the FEV1, FVC, O2, Saturation and dyspnea score (Borg breathlessness score,[BS]) were measured. Fenoterol had no significant effect on pre-exercise spirometry in our patients but maintained a significantly higher level of FEV1 (0.9 +/- 0.1L, p < 0.0001) and FVC (2.0 +/- 0.2L, p < 0.01) immediately after exercise than that after saline control nebulization (0.7 +/- 0.1L, 1.8 +/- 0.2L, respectively). Fenoterol significantly (p < 0.01) increased walking distance (WD) from 201.3 +/- 22.2m to 238.9 +/- 22.2m, but no difference was found in BS and oxygen saturation. The decline in FEV1 following the WT was shown to have an inverse relationship (r = - 0.74, p < 0.002) with the WD improvement (delta WD). Those who walked farther after fenoterol inhalation felt less dyspnea after exercise, also with an inverse correlation (r = -0.61, p < 0.02). These results suggest that fenoterol may improve exercise capacity by preventing airflow deterioration during exercise in patients with COPD. We also recommend the 6-minute walking test in the routine clinical assessment of COPD patients to evaluate the symptomatic benefit offered by betamimetic bronchodilators.

Adrenergic beta-Agonists↗

PubMed1995

Neurogenic goblet cell secretion and bronchoconstriction in guinea pigs sensitised to trimellitic anhydride.

Trimellitic anhydride is a cause of occupational asthma in humans. We have previously found that tracheal instillation of trimellitic anhydride conjugated to guinea pig serum albumin induces acute bronchoconstriction and airway plasma exudation in sensitised animals, responses mediated primarily via histamine release. In the present study, neural mechanisms mediating bronchoconstriction and goblet cell secretion were determined in trimellitic anhydride-sensitised guinea pigs using the ganglionic blocker hexamethonium to eliminate efferent reflex mechanisms, pretreatment with capsaicin to eliminate afferent mechanisms, or cimetidine and mepyramine to eliminate histamine-mediated mechanisms. The magnitude of secretion of intracellular mucus from tracheal goblet cells was quantified morphometrically as a mucus score which is inversely related to the degree of discharge. Guinea pigs were injected intradermally either with 0.1 ml 0.3% trimellitic anhydride in corn oil or with corn oil alone as control. Fourteen to eighteen days later all sensitised animals had developed specific immunoglobulin (Ig) G1 antibodies whereas the controls had not. Tracheal instillation of conjugated trimellitic anhydride in anaesthetised animals significantly increased airway lung resistance (RL) 24-fold in sensitised guinea pigs (34.3 +/- 7.9 cm H2O.ml-1.s) compared with controls (1.4 +/- 0.1 cm H2O.ml-1.s). Mucus score was significantly reduced by 51% (indicating goblet cell secretion) in sensitised guinea pigs (183 +/- 22 mucus score units) compared with controls (372 +/- 41 mucus score units). The antihistamines significantly inhibited conjugated trimellitic anhydride-induced bronchoconstriction by 89%, but did not significantly affect goblet cell discharge. Hexamethonium alone did not significantly affect conjugated trimellitic anhydride-induced bronchoconstriction or goblet cell secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Resistance↗

PubMed1995

Effects of CIS-19, a novel PAF receptor antagonist, on PAF-induced eosinophil recruitment and enhancement of superoxide anion generation in guinea-pigs.

We examined the effects of a novel platelet-activating factor (PAF) receptor antagonist, CIS-19 [cis-2-(3,4-dimethoxyphenyl)-6-isopropoxy-7-methoxyl-1-(N-methylforma mido)- 1,2,3,4-tetrahydronaphthalene], on PAF-induced inflammatory cells recruitment into airways and enhancement of superoxide anion (O2-) generation from cells retrieved by bronchoalveolar lavage (BAL) in urethane-anesthetized guinea-pigs. Administration of PAF (30 ng/kg, i.v.) produced a selective increase of eosinophils into airways, but no significant increase of the number of macrophages, neutrophils or lymphocytes. CIS-19 (2.5 and 5 mg/kg, i.v.) significantly inhibited the eosinophil recruitment induced by PAF. In vitro, PAF, phorbol 12-myristate 13-acetate (PMA) and N-formyl-methionyl-leucyl-phenylalanine (FMLP) directly stimulated generation of O2- from BAL cells in a concentration-dependent manner. CIS-19 (10(-7)-10(-4) M) inhibited production of O2- induced by PAF (10(-7) M) in a concentration-dependent manner with an EC50 value of 0.84 microM, but not induced by PMA (0.5 microgram/ml) or FMLP (10(-7) M). Administration of PAF (5 ng/kg, i.v.) enhanced markedly PMA (0.5 microgram/ml) and FMLP (10(-7) M)-induced generation of O2- by 80.2% and 51.3%, respectively. The enhancing effect of PAF was maximal in cells harvested 5 min after the addition of PAF and then declined to baseline level at 60 min. These responses were inhibited by administration of CIS-19 (0.5-2.5 mg/kg, i.v.) or BN 52021 (5 mg/kg, i.v.). The results indicate that CIS-19 is potent in inhibition of PAF-induced airway inflammatory response and may have therapeutic potential as an anti-inflammatory drugs.

Animals↗

PubMed1995

Sensory neuropeptides modulate cigarette smoke-induced decrease in neutral endopeptidase activity in guinea pig airways.

Cigarette smoke (CS) inhalation stimulates C-fibers to release sensory neuropeptides which mediate airway reflex responses to prevent irritants from entering the lower airways. When CS is inhaled via the upper airways, these airway defense responses may modulate the effect of CS on airway NEP activity and related airway hyperresponsiveness. To examine this possibility, we exposed guinea pigs to 1:10 diluted mid-tar cigarette smoke 100 puffs per day for 7 days and recorded pulmonary resistance of cumulative doses of neurokinin A (NKA, 10(-12)-10(-8) mol/kg, i.v.) or methacholine (Mch, 1-50 micrograms/kg, i.v.). NEP activity in the tracheobronchi was measured using fluorometric assay. Exposure of CS alone failed to alter the dose-response to NKA or Mch compared with air control. NEP activity in the airways after CS exposure was slightly but significantly lower than that of air control. Capsaicin pretreatment 1 week before CS exposure significantly shifted the dose-response curves of NKA, but not Mch, to the left and decreased NEP activity in the airways to a greater extent compared with CS exposure alone group. Capsaicin pretreatment alone failed to alter the responsiveness to NKA or NEP activity. CS also induced a significant increase in neutrophil counts in airways. Capsaicin pretreatment enhanced the effect of CS on neutrophil recruitment. We conclude that sensory neuropeptides may have a protective role in modulation of airways NEP activity downregulation induced by CS, probably by preventing CS from entering the lower airways or the chronic release of sensory neuropeptides induced by CS providing increased amount of substrata for NEP upregulation, and therefore modify the direct effect of CS on NEP activity and related airway hyperresponsiveness.

Airway Resistance↗

PubMed1995

Effect of nasal continuous positive airway pressure on methacholine-induced bronchoconstriction.

Bronchial hyper-responsiveness is a cardinal feature of asthma. To determine whether nasal continuous positive airway pressure (NCPAP) influences airway smooth muscle in response to exogenous stimuli, we examined the effect of NCPAP on aerosolized methacholine-induced bronchoconstriction in 16 stable asthmatic patients. The dose-response curve for each subject was measured by a log transformation and linear regression analysis as well as a formula fitted to the data points to obtain values for a (slope) and b (position). The PD20FEV1 significantly increased in patients receiving 8 cmH2O of NCPAP by one doubling dose compared with that in patients using sham pressure. NCPAP shifted the dose-response curves to be flatter, deviated upwards and to the right. The coefficient a, indicating bronchial reactivity, was significantly lower in patients receiving NCPAP. The coefficient b, indicating the bronchial sensitive threshold, was higher after applying NCPAP. In contrast, coefficients a and b did not change in subjects with sham pressure. NCPAP also significantly enhanced the bronchodilator effect of inhaled salbutamol in response to methacholine-induced bronchoconstriction. In summary, we have shown that NCPAP therapy improves bronchial smooth reactivity with an increase in PD20FEV1 and a reduction in the bronchial reactivity and bronchial sensitivity. Therefore, NCPAP may provide an adjuvant therapy in patients with acute bronchial asthma.

Acute Disease↗

PubMed1995

Multiple brushings with immediate Riu's stain via flexible fibreoptic bronchoscopy without fluoroscopic guidance in the diagnosis of peripheral pulmonary tumours.

BACKGROUND: Accurate diagnosis of peripheral pulmonary lesions usually relies on fluoroscopic guided procedures. As fluoroscopy is not routinely available in many respiratory units, an approach not using fluoroscopy but with a high diagnostic yield is highly desirable. METHODS: Immediate cytological examination of multiple brushings using Riu's stain, a modified Wright's stain, was performed in 38 patients with peripheral pulmonary lesions not visible at bronchoscopy. The results were compared with the final diagnoses determined by histological examination or subsequent Papanicolaou staining of cytological specimens and clinical course. RESULTS: Of the 38 patients 29 were subsequently confirmed to have a malignant tumour. Our method provided a diagnosis of malignancy in 86% of these lesions. The accuracy (91%) and sensitivity (88%) were higher for lesions > 3 cm in diameter than for those of diameter < or = 3 cm (87% and 83%). There were no false positive results. The 29 lesions correctly diagnosed as malignant by Riu's stain required significantly fewer brushings (mean (SD) 3 (2)) than the nine benign lesions (5 (4)). CONCLUSIONS: This technique provides a high diagnostic yield, avoids the need for fluoroscopy, and is probably safer than percutaneous biopsy.

Adenocarcinoma, Bronchiolo-Alveolar↗

PubMed1995

Relation of bronchoalveolar lavage T lymphocyte subpopulations to rate of regression of active pulmonary tuberculosis.

BACKGROUND: Effective host defence against mycobacterial infection chiefly depends on the interactions between macrophages and T lymphocytes. This study investigated the relation of cellular components and their activity of cells obtained by bronchoalveolar lavage (BAL) from the lower respiratory tract to disease regression in patients with active pulmonary tuberculosis without HIV infection. METHODS: Clinical indices including age, sex, the presence of diabetes, fever, the presence of resistant strains of mycobacteria, the bacterial load in sputum, and disease extent on chest radiography at presentation were assessed before commencing four-drug antituberculous therapy. Twenty two patients with active pulmonary tuberculosis were divided into rapid, intermediate, and slow regression groups. Subpopulations of alveolar macrophages separated using discontinuous Percoll density gradient centrifugation and T lymphocytes (with CD3, CD4, CD8, and CD25 monoclonal antibodies) were quantified. RESULTS: There were no differences among rapid, intermediate, and slow regression groups in terms of age, sex, the presence of diabetes, the presence of resistant strains of mycobacteria, or the bacterial load in sputum. No differences were found between the groups in terms of subpopulations of alveolar macrophages or numbers of CD3 and CD4 lymphocytes. By contrast, an increase in CD8 cells was shown in the slow regression group compared with the rapid and intermediate regression groups. CD25 cell numbers were increased in the rapid regression group compared with the slow regression group. The CD4/CD8 ratio was decreased in the slow regression group compared with the rapid and intermediate regression groups and the relation between the proportion of CD25 cells and the CD4/CD8 ratio in BAL fluid was significant. CONCLUSIONS: A decreased CD4/CD8 ratio with an increase in CD8 cells in the alveolar spaces was associated with slow disease regression in patients with active pulmonary tuberculosis without HIV infection, suggesting that the balance of T lymphocyte subsets may play a central part in the modulation of host defence against mycobacterial infection.

Antitubercular Agents↗

PubMed1995

Hypereosinophilia in hemodialysis patients.

Hypereosinophilia (EO) is frequently observed in hemodialysis patients without apparent etiology. We prospectively studied hemodialysis (HD) patients during the period between May 1989 and December 1992, and divided the patients into 3 groups: non-eosinophilic control (EOC), intermittent EO (EOI), and persistent EO (EOP), according to the longterm measurements of their blood eosinophil counts. There were 91 patients enrolled in the study which were followed up for 24 months with 23 patients (25.3%) in the EOC group, 53 patients (58.2%) in EOI group, and 15 patients (16.5%) in the EOP group. There were no significant contribution of the type or reuse of the hemodialyzer to the development of EO, neither were age, serum albumin, KT/V, protein catabolic rate (PCR), or the duration of HD. The functional studies of eosinophils showed no significant difference in hypodense eosinophil distribution or eosinophilic cationic protein (ECP) levels between EOP group and EOC group. The distribution of hypodense eosinophils and serum ECP levels before and after dialysis procedure were not uniform, increasing in some but decreasing in the others. Thus the cause of EO is not merely due to the uremic state or dialysis procedures.

Adult↗

PubMed1994

Vagal stimulation induces increased pulmonary vascular permeability in guinea pig.

The effects of vagal stimulation on pulmonary vascular permeability were studied in guinea pigs in vivo using 125I-labeled albumin as a marker of plasma extravasation. Bilateral vagus nerve stimulation (NS) significantly increased the plasma leakage index in both parenchyma and tracheobronchial tissues. The NS-induced plasma leakage in the parenchyma was unaffected by the alpha-adrenoceptor antagonist phentolamine, the muscarinic receptor antagonist atropine, the ganglionic blocker hexamethonium, or pretreatment with 6-hydroxydopamine or capsaicin, but it was significantly potentiated by the beta-adrenoceptor antagonist propranolol. NS-induced tracheobronchial vascular leakage was markedly inhibited by pretreatment with atropine, hexamethonium, or capsaicin, although it was unaffected by pretreatment with phentolamine, propranolol, or 6-hydroxydopamine. By itself, NG-nitro L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) synthase, had no effect on pulmonary vascular leakage, but it significantly enhanced the NS-induced plasma leakage to parenchyma in a dose-related and L-arginine-reversible manner. Elevation of blood pressure to a similar extent as that induced by L-NAME by a phenylephrine infusion had no significant effect on the increased plasma leakage induced by NS. These results suggest that vagal stimulation increases plasma extravasation in lung parenchyma through the release of unidentified transmitter(s) in a process that is modulated by endogenous NO and catecholamines (via activation of beta-adrenoceptors), and that different mechanisms are involved in the vagally induced plasma extravasation in the pulmonary and tracheobronchial vascular beds.

Animals↗

PubMed1994

Hypodense eosinophil number relates to clinical severity, airway hyperresponsiveness and response to inhaled corticosteroids in asthmatic subjects.

The phenotypically distinct low-density eosinophil, with its greater inflammatory potential, is increased in asthma. However, the role of hypodense eosinophils in the development of asthma is still unclear. We conducted a double-blind, placebo-controlled study to examine the effect of inhaled corticosteroids on the number of hypodense eosinophils in 27 asthmatic subjects and its relationship with clinical severity. The density profile of eosinophils in the peripheral blood was determined using Percoll density gradient fractionation. Eosinophils recovered from asthmatics were mainly in the lower density fractions (< 1.095 g.ml-1) (63 +/- 3%; n = 27), significantly different from those of normal subjects (27 +/- 2%; n = 7). The proportion of hypodense eosinophils was inversely related to the provocative concentration of methacholine producing a 20% fall in forced expiratory volume in one second (PC20) value (r = -0.75). Patients with mild asthma had a lower percentage of hypodense eosinophils (45 +/- 4%; n = 14) than those with moderate asthma (67 +/- 3%; n = 13). Inhalation of budesonide (800 micrograms.day-1) (n = 15) for 4 weeks, but not placebo, significantly improved the PC20 values by 0.97 doubling dose, forced expiratory volume in one second (FEV1) % predicted by 17%, and peak expiratory flow rate (PEFR) by 15%, and decreased PEFR diurnal variability by 5.4%. The percentage of hypodense eosinophils was significantly decreased from 68 +/- 4 to 47 +/- 4% in the budesonide group (n = 15), but not in the placebo group (n = 12) (63 +/- 4 to 65 +/- 4%).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗

PubMed1993

Alveolar macrophage subpopulations in patients with active pulmonary tuberculosis.

Alveolar macrophages are a heterogeneous cell population. The heterogeneity of alveolar macrophages recovered by bronchoalveolar lavage (BAL) from 12 patients with active pulmonary tuberculosis (TB) and 10 normal subjects was studied using Percoll density fractionation. The numbers and subsets (on the basis of CD3, CD4, and CD8 monoclonal antibodies) of lymphocytes in BAL were measured by flow cytometry. Alveolar macrophages recovered from patients with TB were mainly in the lower-density fractions (< 1.030 and 1.030 to 1.040 g/ml), whereas alveolar macrophages from normal subjects were in the higher-density fractions (1.050 to 1.070 and > 1.070 g/ml). There were no significant differences in alveolar macrophages' repartition between smokers and nonsmokers in either patients with TB or normal subjects. The significant changes in the proportions of the lowest fraction and the higher fractions of alveolar macrophages in patients with TB were not altered after division of our patients into smoker and nonsmoker subgroups when compared with corresponding subgroups in normal subjects. The proportion of the alveolar macrophages in the lowest fraction was inversely related to the bacterial load of sputum and the disease extent on chest radiography in TB patients. The CD4/CD8 ratio was significantly higher in patients with TB. This study shows that alveolar macrophages from TB patients are heterogeneous with hypodense cells predominant probably by interaction with T lymphocytes. Changes in the proportions of alveolar macrophages within subpopulations may be of critical importance in determining the overall response of the lung to TB infection.

Bronchoalveolar Lavage Fluid↗

PubMed1993

Relationship between increased hypodense eosinophils in the peripheral blood and bronchial hyperresponsiveness in patients with bronchial asthma.

Eosinophils are the most prominent inflammatory cells involved in the development of bronchial hyperresponsiveness in bronchial asthma. There is evidence that eosinophils in the peripheral blood are a heterogeneous cell population. The heterogeneity of eosinophils in the peripheral blood from 16 patients with mild to moderate bronchial asthma and seven normal subjects was studied using Percoll density fractionation. Eosinophils recovered from patients with bronchial asthma were mainly in the lower density fractions (< 1.095 g/mL), whereas eosinophils from normal subjects were in the higher density fractions (> 1.095 g/mL). The total cell count and the proportion of hypodense eosinophils were highly correlated with the provoking concentration (PC20) of methacholine, which caused a 20% decrease in FEV1 but not in the baseline spirometry. Disease severity, determined on the grounds of clinical history and the peak expiratory flow rate as well as its variability, showed that patients with moderate bronchial asthma had a higher count of hypodense eosinophils than those with mild bronchial asthma. This study shows that eosinophils from asthmatics, when compared with those from control subjects, are heterogeneous and predominantly hypodense cells. Changes in the repartition of the eosinophil subpopulations may be of critical importance in determining the magnitude of the inflammatory response of the airways in bronchial asthma.

Adolescent↗

PubMed1992

The effect of endogenous nitric oxide on neurogenic plasma exudation in guinea-pig airways.

We studied the effect of endogenous nitric oxide (NO) on vagally induced plasma exudation into guinea-pig trachea and main bronchi using 125I-albumin as a plasma marker. NG-Nitro-L-arginine methyl ester (L-NAME, 1-10 mg/kg) dose dependently inhibited neurogenic plasma exudation. Intravenous phenylephrine which simulated the vasopressor effect as L-NAME (10 mg/kg) was without effect. The effect of L-NAME (5 mg/kg) was reversed by L-arginine (50 mg/kg). These results suggest that endogenous NO may contribute to neurogenic inflammation in the airways.

Animals↗

PubMed1992

K+ channel activator inhibition of neurogenic goblet cell secretion in guinea pig trachea.

A potassium (K+) channel activator, BRL 38227, inhibited goblet cell secretion in guinea-pig trachea induced by either electrical stimulation of the vagus nerves or acute inhalation of cigarette smoke, two stimuli which activate both cholinergic nerves and capsaicin-sensitive sensory nerves. BRL 38227 failed to inhibit methacholine- or substance P-induced goblet cell secretion which suggests that K+ channel activators inhibit neurogenic goblet cell secretion via a prejunctional effect on cholinergic and sensory nerves.

Animals↗

PubMed1992

Differential inhibitory effects of opioids on cigarette smoke, capsaicin and electrically-induced goblet cell secretion in guinea-pig trachea.

1. Goblet cell secretion in guinea-pig airways is under neural control. Opioids have previously been shown to inhibit neurogenic plasma exudation and bronchoconstriction in guinea-pig airways. We have now examined the effects of morphine and opioid peptides on tracheal goblet cell secretion induced by either electrical stimulation of the cervical vagus nerves, exogenous capsaicin, or acute inhalation of cigarette smoke. The degree of goblet cell secretion was determined by a morphometric method and expressed as a mucus score which is inversely related to mucus discharge. 2. Morphine, 1 mg kg-1, completely blocked goblet cell secretion induced by electrical stimulation of the vagus nerves. Morphine also inhibited the response to cigarette smoke given either at a low dose (10 breaths of 1:10 diluted in air), which principally activates cholinergic nerves, or at a high dose (20 breaths of undiluted), which activates capsaicin-sensitive sensory nerves, by 100% and 73% respectively. In contrast, morphine had no significant inhibitory effect on capsaicin-induced goblet cell secretion. The inhibitory effect of morphine was reversed by naloxone. 3. Selective mu- or delta-opioid receptor agonists, [D-Ala2, NMePhe4, Glyol5]enkephalin (DAMGO) or [D-Pen2, D-Pen5]enkephalin (DPDPE) respectively, caused a dose-related inhibition of low dose cigarette smoke-induced goblet cell discharge, with DPDPE more potent than DAMGO. A kappa-receptor agonist, trans-3,4-dichloro-N-methyl-N-(2-(1-pyrollidinyl)cyclohexyl) benzeneacetamine (U-50,488H), had no inhibitory effect. DPDPE had no inhibitory effect on goblet cell secretion induced by exogenous methacholine. 4. DAMGO dose-dependently blocked the response to high dose cigarette smoke with a maximal inhibition of 95% at 2 x 10(-7) mol kg-1. Neither DPDPE nor U-50,488H had any significant inhibitory effect. The increase in goblet cell secretion induced by exogenous substance P was not affected by DAMGO.5. We conclude that opioids inhibit neurally-mediated goblet cell secretion via actions at prejunctional delta and mu-receptors on cholinergic nerves and at mu-receptors on sensory nerve endings, and that capsaicin activation of sensory nerves is via a different mechanism from that of electrical or cigarette smoke activation.

Animals↗