Biomedical subjects

K Shirato

Publications and source records attributed to K Shirato.

At least 163 records · Page 9Linked to original sources

PubMed1996

Effects of spontaneous myocardial oscillation on cardiac function: direct observation of the epicardial fluorescence image in calcium overloaded isolated hamster hearts.

OBJECTIVES: Calcium overload induces spontaneous cyclic calcium release from the sarcoplasmic reticulum, leading to spontaneous myocardial oscillation. This study was designed to elucidate (1) the effect of the myocardial oscillation on changes in ventricular performance and (2) how these changes relate to the strength of the diastolic spontaneous myocardial oscillation and the spatial extent--that is, in how extensive an area of the epicardium it occurred. METHODS: the isovolumic pressure of the left ventricle and epicardial fura 2 fluorescence in isolated hamster hearts were simultaneously observed at various calcium concentrations ([Ca2+]o). Endothelial cells and pericytes of the capillaries, preferentially stained by fura 2, were passively oscillated by surrounding myocytes during diastole at concentrations greater than 1 mmol/l of [Ca2+]o. The strength of the myocardial oscillation was evaluated as the root mean square (RMS) of fluctuation in the distance between endothelial cells or pericytes. The spatial extent of the myocardial oscillation was estimated as the appearance rate, defined as the ratio of the number of microscopic fields showing the capillary oscillation, to the total number of examined fields. RESULTS: Up to 4 mmol/l of [Ca2+]o, developed pressure and maximum rate of pressure rise significantly increased in a manner dependent on [Ca2+]o, but a further increase in [Ca2+]o significantly decreased these parameters. In the presence of ryanodine (2.5 mumol/l), developed pressure and maximum rate of pressure rise monotonously increased in a manner dependent on [Ca2+]o. Although the oscillation was never observed at 1 mmol/l of [Ca2+]o (appearance rate = 0%), it occurred in some of the microscopic fields at 2 and 4 mmol/l (appearance rate = 19.5 and 56.3%, respectively) and occurred in all microscopic fields at concentrations greater than 4 mmol/l (appearance rate = 100%). Ryanodine, which completely eliminated the capillary oscillation, inhibited the increase of both RMS and end-diastolic pressure by an increase in [Ca2+]o. CONCLUSIONS: Our data suggest that the myocardial oscillation impairs systolic and diastolic function in intact ventricle, and that these effects are associated with the spatial extent and the strength of the myocardial oscillation.

Animals↗

PubMed1996

The effect of diastolic vibration on the relaxation of rat papillary muscle.

OBJECTIVE: It has been demonstrated that the application of an external mechanical vibration during the ventricular relaxation phase of the heart (diastolic vibration) decreases the time needed for myocardial relaxation. The objective of this study is to see whether this vibration-induced decrease in relaxation time is an intrinsic property of the contractile proteins. We hypothesize that this decrease in duration of the late systolic phase by diastolic vibration is likely to be due to a forced detachment of crossbridges from the actin filament. This would then result in a decrease in the relaxation time of myocardial tissue. METHODS: A controlled vibration of variable amplitude and frequency was applied to isolated twitching rat papillary muscles. Vibration was initiated from directly after peak tension development and ended when tension had returned to baseline. Effects of applied vibration were expressed as changes in the time interval from 90% rising- to 50% falling-force level, which was termed the 'late systolic phase'. RESULTS: The data showed that in general diastolic vibration decreased the duration of this late systolic phase. A vibration of 1.0% of Lmax at 50 Hz in the late systolic phase shortened this period by 27 ms (20-30%) on average. At increasing amplitude of vibration the increase in the rate of relaxation was even more pronounced. Shortening of this duration was slightly less at frequencies of vibration below 40 Hz than at higher frequencies of vibration. Changes in the resting muscle length did not result in significant changes in shortening of the studied relaxation period. CONCLUSION: The results show that relaxation is accelerated during application of an external vibration during the period of tension fall of an isolated cardiac muscle preparation. Therefore, we can conclude that the acceleration of relaxation due to vibration is primarily due to properties of the myocytes themselves rather than to the complex geometric structure of the heart. Tension in the relaxation phase was reduced during diastolic vibration, which suggests that the number of crossbridges bound to the actin filament was reduced by the length perturbation.

Animals↗

PubMed1996

Coronary angioplasty ameliorates hypoperfusion-induced endothelial dysfunction in patients with stable angina pectoris.

OBJECTIVES: This study sought to investigate the effect of coronary angioplasty on chronic hypoperfusion-induced endothelial dysfunction in patients with coronary heart disease. BACKGROUND: The endothelium is an important component for organ flow regulation. Ischemia with or without reperfusion is known to cause endothelial dysfunction. We tested the hypothesis that chronic hypoperfusion impairs endothelial function in the angiographically normal coronary artery segment distal to stenosis and that the impairment by chronic hypoperfusion is reduced by coronary angioplasty. METHODS: In 13 patients with stable angina pectoris, substance P (10, 30 and 100 pmol) and nitroglycerin (200 micrograms) were sequentially infused into the coronary artery in a cumulative manner on the day after coronary angioplasty. In 10 of these patients, vascular responses to these agents were again investigated 3 months after angioplasty. Changes in vascular diameter were evaluated in vessels located proximal and distal to the target lesion, both of which were angiographically normal, by performing computer-assisted quantitative coronary angiography. In five patients, the transstenotic pressure gradient was also measured with a pressure sensor-mounted guide wire before angioplasty. RESULTS: On the day after angioplasty, the magnitude of dilation by substance P in distal segments was significantly less than that in proximal segments and inversely correlated with the transstenotic pressure gradient (p < 0.05) and lesion stenosis (p < 0.05). There was no difference in nitroglycerin-induced vasodilation between the two vessel segment groups. Three months later, the impaired response to substance P in the distal segment was restored to normal. CONCLUSIONS: We conclude that chronic hypoperfusion impairs endothelium-dependent dilation of coronary artery distal to critical stenosis in patients with ischemic heart disease and that coronary angioplasty ameliorates the endothelial dysfunction within 3 months.

Aged↗

PubMed1996

Endogenous nitric oxide modifies antigen-induced microvascular leakage in sensitized guinea pig airways.

To examine the role of endogenous nitric oxide in allergic airway inflammation, we investigated the effect of a nitric oxide synthase inhibitor, N omega-nitro-L-arginine methyl ester (l-NAME), on antigen-induced airway microvascular leakage in actively sensitized guinea pigs by using Evans blue dye. Three weeks after sensitization with ovalbumin (10 micrograms), the tracheas were cannulated, and lungs were artificially ventilated. Animals were pretreated with atropine and propranolol (both 1 mg/kg, intravenously) to avoid neural modification. Ovalbumin inhalation (3 mg/ml, 1 minute) challenge caused significant microvascular leakage in all airways portions, which was significantly suppressed in a dose-dependent manner by pretreatment with intravenous injection of L-NAME (1 and 10 mg/kg) but not with the inactive enantiomer D-NAME (10 mg/kg). This inhibition by L-NAME was significantly reversed by co-administration of L-arginine (100 mg/kg, intravenously). Pretreatment with a vasoconstrictor, phenylephrine (20 micrograms/kg, intravenously), had no inhibitory effects on antigen-induced airway microvascular leakage despite increasing systemic blood pressure. Inhalation of representative mast cell-derived mediators, histamine (2 mg/ml, 1 minute) or leukotriene D4 (5 micrograms/ml, 1 minute), produced significant microvascular leakage in all airways. L-NAME (10 mg/kg, intravenously) partially but significantly inhibited leukotriene D4-induced leakage, whereas histamine-induced leakage was not affected. These results suggest that endogenous nitric oxide acts to increase airway microvascular leakage after airway allergic reaction.

Animals↗

PubMed1996

Angiotensin converting enzyme (ACE) inhibitor-induced cough and substance P.

BACKGROUND: Angiotensin converting enzyme (ACE) inhibitors cause coughing in 5-10% of patients, but the exact mechanisms of this effect are still unclear. In the airways ACE degrades substance P so the cough mechanism may be related to this peptide. METHODS: Nine patients who developed a cough and five patients who did not develop a cough when taking the ACE inhibitor enalapril (2.5 or 5.0 mg/day) for hypertension were enrolled in the study. No subjects had respiratory disease and the respiratory function of all subjects was normal. One month after stopping enalapril, inhalation of hypertonic saline (4%) was performed using an ultrasonic nebuliser for 15-30 minutes to induce sputum. The concentration of substance P in the sputum sample was measured by radioimmunoassay. In four of the nine cases with a cough enalapril was given again for 1-2 weeks and the concentration of substance P in the induced sputum was again measured. RESULTS: One month after stopping enalapril the mean (SE) concentration of substance P in the sputum of the group with a cough was 16.6 (3.0) fmol/ml, significantly higher than that in the subjects without a cough (0.9 (0.5) fmol/ml). All four subjects in the group with a cough who were given a repeat dose of enalapril developed a cough again, but the concentrations of substance P in the induced sputum while taking enalapril (17.9 (3.2) fmol/ml) were similar to the values whilst off enalapril (20.0 (2.5) fmol/ml). CONCLUSIONS: The mechanisms of ACE inhibitor-induced coughing may involve substance P mediated airway priming. However, the final triggering of the ACE inhibitor-induced coughing is unlikely to be due to this peptide.

Aged↗

PubMed1996

Bradykinin regulation of airway submucosal gland secretion: role of bradykinin receptor subtype.

To clarify the role of bradykinin receptor subtypes, we examined the effect of bradykinin on feline tracheal and human airway submucosal gland secretion using an isolated gland preparation. Bradykinin induced a significant increase in [3H]glycoconjugate secretion in a dose-dependent manner from isolated glands, which was significantly inhibited by D-Arg-(Hyp3, Thi5,8, D-Phe7)-bradykinin (the B2-receptor antagonist), whereas Des-Arg9-(Leu8)-bradykinin (B1-receptor antagonist) or indomethacin did not significantly alter it. Nitric oxide synthase inhibitor (nitro-L-arginine methyl ester) caused a significant inhibition of bradykinin-induced glycoconjugate secretion, which was reversed by the addition of L-arginine. Bradykinin evoked bidirectional current responses, and an initial inward current (Cl- current) was followed by an outward current (K+ current) of the acinar cells in a whole cell configuration by patch-clamp technique. Bradykinin induced an immediate increase in intracellular calcium concentration ([Ca2+]i) of the acinar cells followed by a prolonged plateau, and Ca2+ removal resulted in an initial increase alone. [Ca2+]i rise was significantly inhibited by the B2-receptor antagonist, whereas the B1-receptor antagonist did not significantly alter it. These findings suggest that B2-receptor stimulation and the resultant [Ca2+]i rise induced both mucus glycoprotein and electrolyte secretions, involving NO formation in airway submucosal gland cells.

Animals↗

PubMed1996

Eosinophil adhesion to cultured airway epithelial cells from guinea pig lungs.

We examined the effects of histamine, tumor necrosis factor-alpha (TNF alpha), interferon-gamma (IFN gamma), indomethacin and dexamethasone on the adherence of eosinophils to airway epithelial cells. Epithelial cells were isolated from guinea pig trachea through enzymatic digestion, and cultured until they showed confluence. Eosinophils were taken by peritoneal lavage from guinea pigs sensitized with horse serum and purified. The adhesion of eosinophils to cultured epithelial cells was examined using 51Cr. The percentage adhesion was obtained by dividing counts per minute of lysed eosinophils adhered to epithelial cells by suspended eosinophils. Histamine significantly increased the adhesion of eosinophils to epithelial cells, while TNF alpha or IFN gamma did not significantly alter the adhesion. Indomethacin significantly inhibited the adhesion of eosinophils to epithelial cells in both nontreated and histamine-induced conditions. Dexamethasone also reduced adhesion, although it did not reach statistical significance. These findings indicate that histamine induced eosinophil adherence to airway epithelial cells, suggesting a role of endogenous prostaglandins in adherence.

Animals↗

PubMed1996

Morphologic aspects of airways of patients with pulmonary emphysema followed by bronchial asthma-like attack.

Morphometric analysis of airways was performed in autopsied lungs from four patients with pulmonary emphysema (PE) followed by bronchial-asthma (BA)-like attacks (Group PE+BA) (four males, 72 +/- 9 yr). The results were compared with those from five pulmonary emphysema patients (Group PE) (five males, age 71 +/- 4 hr), three patients with bronchial asthma (Group BA) (one female and two males, age 65 +/- 7 yr), and four control subjects with no pulmonary diseases (Group Cont) (one female, three males, age 64 +/- 4 yr). The proportion of gland area to bronchial wall (gland%), ratio of goblet-cell occupancy to the total epithelial layer (goblet%), thickness of the basement membrane, amount of intraluminal mucus (mucus occupying ratio; MOR%), and number of various cell types per square millimeter in airway walls in a section 4 microns thick were measured in central (3 to 8 mm diameter) and peripheral airways (2 mm or less diameter). Gland% for the PE+BA group was significantly greater than that for the Cont group, whereas it did not differ significantly from that of the PE or BA groups. Goblet% and thickness of the basement membrane in central and/or peripheral airways in Group PE+BA were significantly greater than those in Group Cont, whereas those in Group PE were similar to those in Group Cont. Although not statistically significant, MOR% in central and peripheral airways from Group PE+BA showed a similar value to that in Group BA, whereas MOR% in Group PE was the same as that in Group Cont. The eosinophil number in peripheral airways walls in Group PE+BA showed a similar value to that in Group BA, which was significantly greater than in Group Cont. Other cells (macrophages, lymphocytes, and neutrophils) showed similar values among Groups PE+BA, PE, and BA. The number of eosinophils in central and/or peripheral airways correlated significantly with both goblet% and BMT, whereas other cells did not. These findings indicate that the airways of Group PE+BA are morphologically similar to those of Group BA, suggesting a combination of pulmonary emphysema with bronchial asthma.

Aged↗

PubMed1996

A neurokinin 1-receptor antagonist improves exercise-induced airway narrowing in asthmatic patients.

Recent reports suggest the involvement of vascular phenomena in exercise-induced asthma. Sensory neuropeptides, such as substance P (SP), which causes airway vascular dilatation and plasma leakage, have been demonstrated to play a role in hyperpnea-induced airway narrowing in animal studies. The purpose of this study was to investigate the importance of tachykinins in exercise-induced airway narrowing in patients with asthma using a selective neurokinin 1-receptor (NK1-receptor) antagonist, FK-888. In a double-blind, placebo-controlled, crossover trial, nine subjects with stable asthma were given FK-888 (2.5 mg) or placebo by inhalation 20 min before each exercise at a level previously demonstrated to cause a fall of at least 40% in specific airway conduction (SGaw). Inhalation of FK-888 had no significant effect on baseline SGaw. While the recovery from exercise-induced airway narrowing was significantly faster after treatment with FK-888 the area under the curve for SGaw during the 50 min after exercise was significantly reduced (p<0.05) and the time taken for the SGaw to recover to within 65% of baseline after exercise was also significantly shorter with FK-888 than the placebo (p<0.05). However, treatment with FK-888 did not significantly attenuate the maximal fall in SGaw. These results suggest that NK1-receptor-mediated mechanisms are involved in the recovery phase of exercise-induced airway narrowing. The possible mechanisms of these phenomena are discussed.

Administration, Inhalation↗

PubMed1996

Aerosolized human neutrophil elastase induces airway constriction and hyperresponsiveness with protection by intravenous pretreatment with half-length secretory leukoprotease inhibitor.

This study was designed to determine the effects of inhaled human neutrophil elastase (HNE) on airway constriction and airway responsiveness, and to examine the protection by an intravenous recombinant half-length secretory leukoprotease inhibitor, r1/2SLPI in guinea pigs. Aerosol inhalation of HNE (250 microgram/ml, for 3 min) caused a transient but significant airway constriction, in which lung resistance (RL) increased from 194 +/- 18 (mean +/- SEM) to 461 +/- 42 cm H2O/L/s (p < 0.001). Thirty minutes after the end of HNE inhalation, airway responsiveness to intravenous 5-hydroxytryptamine (5-HT) was significantly increased. The provocative dose causing a 200% increase in RL (PD200) was significantly decreased from 10.0 +/- 1.2 to 6.5 +/- 0.8 microgram/kg (p < 0.001). Forty-five minutes after the end of HNE inhalation, total cells in bronchoalveolar lavage fluid (BALF) were significantly increased (p < 0.05). Histologic study of intrapulmonary bronchi demonstrated an acute inflammatory response characterized by damage to the epithelium, airway obstruction by mucus plugs, and recruitment of mononuclear and polymorphonuclear cells to the bronchial epithelium. r1/2SLPI (30 mg/kg) injected 5 min before the initiation of HNE inhalation significantly inhibited the airway constriction (p < 0.05), the airway hyperresponsiveness (p < 0.01), and the increase of cells in BALF (p < 0.05). The present data suggest that HNE plays a role in the induction of airway constriction and airway hyperresponsiveness in various inflammatory lung diseases with pulmonary neutrophil infiltration, such as chronic obstructive pulmonary diseases (COPD) and possibly bronchial asthma. r1/2SLPI may be useful as an antiprotease treatment.

Aerosols↗

PubMed1996

N-acetylcysteine inhibits loss of diaphragm function in streptozotocin-treated rats.

We examined whether streptozotocin (STZ)-induced diabetic rats have an impairment in diaphragm contractility, and if so, whether N-acetylcysteine (NAC), a nonspecific antioxidant, prevents this impairment. First, diaphragm contractility, assessed by tension-frequency relationships and twitch kinetics in in vitro diaphragm strip preparations of Wistar rats, was obtained on Days 3 and 7 after administration of STZ of 30 or 60 mg/kg body weight, and compared with that of the control group. Second, NAC at 500 mg/kg body weight or vehicle solution was administered orally every day in rats treated with STZ at 60 mg/kg body weight, and diaphragm function on Day 7 after starting NAC treatment was compared between vehicle control and STZ-treated groups. We found that diaphragm function in STZ-treated rats, which had hyperglycemia, decreased in a dose- and time-dependent manner. NAC inhibited the decrease in diaphragm contractility in STZ-treated rats without reducing blood glucose. These findings suggest that the loss of diaphragm function in STZ-induced diabetic rats is not directly related to hyperglycemia. The data are consistent with secondary alterations of normal cytokine signaling or changes in the redox state of the cell, both of which could be affected by NAC treatment.

Acetylcysteine↗

PubMed1996

Incubation with IgE increases cholinergic neurotransmission in human airways in vitro.

Airway cholinergic hyperresponsiveness is frequently observed in asthmatic patients. Recent reports suggest the possible involvement of IgE in hyperresponsiveness, although the exact mechanism is still uncertain. In this study, we examined whether incubation with IgE could facilitate the cholinergic function in human airways. Bronchi were obtained from 20 patients undergoing lung resection. Cholinergic contractile responses were induced by electrical field stimulation (EFS) or exogenous acetylcholine (ACh), and they were assessed by isometric tension measurement. EFS-induced ACh release from cholinergic nerves was also measured by high performance liquid chromatography. Incubation with IgE significantly enhanced EFS-induced bronchial contraction and ACh release as compared with the values of the bronchi incubated with heat inactivated IgE (control) (p < 0.05, respectively), but it did not alter the contractile responses induced by exogenous ACh. Pretreatment with the muscarinic M2-receptor agonist pilocarpine reduced the EFS-induced ACh release in the control tissues (p < 0.05), but not in the tissues incubated with IgE. The M2-receptor antagonist methoctramine significantly enhanced the EFS-induced contraction in control bronchi (p < 0.05), but this augmentation was not observed in the tissues incubated with IgE. These results suggest that IgE itself can enhance cholinergic bronchial contraction via facilitation of ACh release from cholinergic nerves and that this augmentation is related to autoreceptor M2 dysfunction at nerve endings.

Acetylcholine↗

PubMed1996

Nitrogen dioxide exposure increases airway contractile response to histamine by decreasing histamine N-methyltransferase activity in guinea pigs.

To determine the mechanism responsible for nitrogen dioxide (NO2)-induced airway hyperresponsiveness, we examined the effects of NO2 exposure on the contractile response to histamine and the level of histamine N-methyltransferase (HMT) activity, a histamine-degrading enzyme, in guinea pig trachea in vitro. Guinea pigs were divided into seven groups. Each group received continuous NO2 exposure (2.0 ppm) for either 2, 6, 12, 24, 48, or 96 h. The remaining group did not receive NO2 exposure (control). HMT activity in trachea was decreased from the control value of 70.3 +/- 7.7 pmol/min/mg protein to 34.6 +/- 6.7 pmol/min/mg protein by 12 h exposures of NO2. However, 24 and 48 h exposures of NO2 did not significantly alter HMT activity. In contrast, HMT activity exceeded the control value by 96 h exposures of NO2 (85.5 +/- 5.1 pmol/min/mg protein). Twelve hour exposures of NO2 shifted the concentration-response curves to histamine to lower concentrations and significantly reduced the median effective concentration (EC50) of histamine (log M) from the control value of -5.16 +/- 0.09 to -6.15 +/- 0.14 (P < 0.01). In contrast, the EC50 concentration of histamine (log M) increased from the control value of -5.20 +/- 0.10 to -4.90 +/- 0.11 by 96 h exposures of NO2 (P < 0.05). However, NO2 exposure did not alter the contractile response to acetylcholine. Morphologically, tracheal epithelial cells had vacuoles after 12 h exposures of NO2, but denudation of the epithelium did not occur during this experiment. In situ hybridization for HMT mRNA demonstrated that the level of HMT mRNA increased dominantly in tracheal epithelial cells after 96 h exposures of NO2. The present results indicated that the decrease in the level of HMT activity in the trachea was closely associated with the increase in the airway contractile response to histamine, suggesting that NO2-induced transient airway hyperresponsiveness to histamine is due to the decreased capacity of histamine catabolism in airway.

Animals↗

PubMed1996

Transforming growth factor beta 1 (TGF beta 1) gene expression by eosinophils in asthmatic airway inflammation.

The increase in thickness of bronchial walls by such structural changes as subepithelial fibrosis contributes to the severity and chronicity of asthma by amplifying airway narrowing. However, the pathogenesis of this structural alteration is not known. Transforming growth factor beta 1 (TGF beta 1) is known to have biologic activities relevant to the cellular and molecular events in subepithelial fibrosis, such as the deposition of collagen I and III and the increase of myofibroblasts beneath the epithelial basement membrane. Therefore, we examined TGF beta 1 gene expression in bronchial biopsy tissues from five severe asthmatics, five mild asthmatics, and five normal subjects using in situ hybridization combined with histochemical staining. Cells expressing TGF beta 1 mRNA were detected in tissues from four normal subjects, one mild asthmatic, and five severe asthmatics. The density of positive cells in severe asthmatic tissues (52.1 +/- 22.7, mean +/- SD/mm2) was significantly greater than that in mild asthmatic tissues (1.0 +/- 1.9/mm2, P < 0.01) or normal tissues (10.5 +/- 10.6/mm2, P < 0.02). The density in mild asthmatic tissues was not significantly different from that in normal tissues. The vast majority of positive cells in severe (99.1 +/- 1.7%) and mild (100%) asthmatic tissues were identified as eosinophils. In contrast, eosinophils constituted a small portion of positive cells (20.8 +/- 21.6%) in normal tissues. These results indicated that TGF beta 1 mRNA was overexpressed in severe asthmatics and that the main source of the mRNA was eosinophils, suggesting that eosinophils play an important role in the pathogenesis not only of inflammation but also of structural changes, such as subepithelial fibrosis, in asthmatic airways.

Adult↗

PubMed1996

Involvement of endogenous tachykinins in LTD4-induced airway responses.

Leukotriene D4-(LTD4) has been reported to cause tachykinin release from airway sensory nerves. However, the functional significance of endogenously released tachykinins in LTD4-mediated airway responses has not been fully clarified. The aim of this study was to investigate whether LTD4-induced airway responses are due, in part, to tachykinin release in guinea-pigs. Airway plasma exudation and bronchoconstriction were assessed by measuring extravasation of Evans blue dye and by mean pulmonary resistance (RL) in the presence of atropine (1 mg.kg-1 i.v.) and propranolol (1 mg.kg-1 i.v.), respectively. LTD4 (5 micrograms.mL-1 for 1 min) inhalation caused increase in plasma exudation and RL. Capsaicin pretreatment of animals to deplete sensory neuropeptides significantly inhibited LTD4-induced plasma exudation in the main bronchi, but not in the central (cIPA) and peripheral intrapulmonary airways (pIPA). Pretreatment with specific tachykinin neurokinin-1 (NK1)-receptor antagonists, FK 888 (10 mg.kg-1 i.v.) and CP 96345 (4 mg.kg-1 i.v.), also significantly reduced LTD4-induced plasma exudation in the main bronchi, and in the main bronchi and cIPA, respectively. However, these antagonists did not significantly affect the LTD4-induced increase in RL. In contrast, neurokinin-2 (NK2)-receptor antagonist, SR 48968 (0.3 mg.kg-1 i.v.), significantly inhibited the bronchoconstriction after LTD4-inhalation. These results suggest that leukotriene D4-induced bronchoconstriction and plasma exudation in guinea-pigs are, in part, due to tachykinin release from airway sensory nerves.

Administration, Inhalation↗

PubMed1996

Continuity of airway goblet cells and intraluminal mucus in the airways of patients with bronchial asthma.

The aim of this study was to elucidate the mechanism of the formation of the widespread mucous-plugging observed in autopsied lungs from patients with bronchial asthma. We performed morphometric analysis of airways of autopsied lungs from eight patients with bronchial asthma (Group BA), and compared it with those of six chronic bronchitics (Group CB) and four control patients (Control). The following parameters were measured in paraffin sections: volume proportion of bronchial glands to bronchial wall (Gland%); goblet cell granules to total epithelial layer (Goblet %); intraluminal mucus expressed as the mucus occupying ratio (MOR); volume ratio of intraluminal mucus continuous with goblet cells to total intraluminal mucus (Vc/Vtol %); and surface ratio of the contact surface of intraluminal mucus continuous with goblet cells to the total luminal surface (Sc/Stot %). Gland%, Goblet %, and MOR or inflammatory cell numbers in the airway walls both from Group BA and CB were larger than those from the Control group. However, no significant differences were observed between Group BA and CB in Gland%, Goblet %, MOR or inflammatory cell numbers, except for the eosinophil number: i.e. 23 +/- 3, 22 +/- 3 and 6 +/- 2% in Gland%; 22 +/- 9, 5 +/- 4 and 2 +/- 2% in Goblet%; 10 +/- 3, 18 +/- 3 and 0.3 +/- 0.5% in MOR; 199 +/- 68, 10 +/- 3 and 2 +/- 2 cells. mm-2 in eosinophil number of the peripheral airways from Groups BA, CB and Control, respectively. In contrast, marked and significant increases were observed both in Vc/Vtot% and Sc/Stot% in Group BA compared to Groups CB and Control both in central and peripheral airways: i.e. Vc/Vtot% in the peripheral airways was 53 +/- 5, 4 +/- 3 and 0.8 +/- 0.8% from Groups BA, CB and Control, respectively (BA vs CB or BA vs Control, p < 0.01 each). These findings suggest that the continuity of goblet cells and intraluminal mucus or lack of full release of mucus, from goblet cells, is peculiar to asthmatic airways, and may contribute to the formation of mucous-plugs.

Age Factors↗

PubMed1996

Repeated allergen exposure enhances excitatory nonadrenergic noncholinergic nerve-mediated bronchoconstriction in sensitized guinea-pigs.

The effect of repeated allergen inhalation challenge on the airway excitatory nonadrenergic noncholinergic (e-NANC) nerve-mediated bronchoconstrictor response was studied in ovalbumin (OA) sensitized guinea-pigs. Three weeks after sensitization, OA inhalation, 0.03% for 3 min (challenged group), or saline inhalation (control group) was repeated every day for 4 weeks. The e-NANC nerve function was examined in vitro by means of isometric tension measurement of main bronchi. After pretreatment with atropine (10(-6) M) and propranolol (10(-6) M), we performed electrical field stimulation (EFS) or exogenous neurokinin A (NKA) administration. In the challenged group, EFS-induced main bronchial contraction was significantly greater than that of the control group (p < 0.05 or p < 0.01), but exogenous NKA-mediated responses were almost the same in both groups. The e-NANC-induced main bronchial contractions after EFS were enhanced by pretreatment with the neutral endopeptidase inhibitor, phosphoramidon, to the same degree in the control and challenged groups, indicating that the peptide degradation mechanisms were not impaired even in the challenged group. Substance P immunoreactivities in the lung of the challenged group were significantly higher than those of the control group. These results suggest that chronic airway inflammation after repeated allergen challenge increases excitatory nonadrenergic noncholinergic nerve function, possibly by enhancing sensory neuropeptide production and/or release.

Allergens↗

PubMed1996

Surfactant apoprotein-A concentration in airway secretions for the detection of pulmonary oedema.

Patients with cardiogenic pulmonary oedema expectorate foamy sputum containing surfactant, which might be expected to include surfactant apoprotein A (SP-A). SP-A is specific for lung surfactant. We have measured the SP-A concentration in airway secretions to determine whether it is useful in distinguishing pulmonary oedema from other disorders. Samples of sputum and of aspirated airway secretion were obtained from 11 patients with cardiogenic pulmonary oedema, seven patients with clinically stable congestive heart failure, five patients with adult respiratory distress syndrome (ARDS) and 20 control patients (10 intubated) with other respiratory diseases. The samples were used for the measurement of SP-A concentration by a two-site simultaneous immunoassay with monoclonal antibodies against SP-A. SP-A concentrations, measured in samples of sputum and aspirated secretions, depended on the diagnosis of the patients from which they had come. In descending order these samples came from patients with: cardiogenic pulmonary oedema (1324 +/- 197 micrograms.mL-1; n = 33); ARDS (311 +/- 47 micrograms.mL-1; n = 23); clinically stable congestive heart failure (78 +/- 10 micrograms.mL-1; n = 21); and control conditions (3.0 +/- 0.6 micrograms.mL-1; n = 30). Concentrations from disease samples did not overlap with controls. In samples from patients with cardiogenic pulmonary oedema, the SP-A concentration correlated with mean pulmonary capillary wedge pressure (PCWP) (p < 0.001; n = 39). These findings indicate that the measurement of the surfactant apoprotein A concentration in airway secretions may be useful for the detection of pulmonary oedema.

Aged↗