Pulmonary pharmacology最新文献_第3页

Inhalation Cough Challenge in the Investigation of the Cough Reflex and Antitussives 吸入性咳嗽对咳嗽反射和止咳药的影响

Pulmonary pharmacology Pub Date : 1996-10-01 DOI: 10.1006/pulp.1996.0036

A.H. Morice

引用次数: 41

Pulmonary pharmacology Pub Date : 1996-10-01 DOI: 10.1006/pulp.1996.0042

Kiyohisa Sekizawa , Yu Xia Jia , Takae Ebihara , Yuko Hirose , Yoshitaka Hirayama , Hidetada Sasaki

{"title":"Role of Substance P in Cough","authors":"Kiyohisa Sekizawa , Yu Xia Jia , Takae Ebihara , Yuko Hirose , Yoshitaka Hirayama , Hidetada Sasaki","doi":"10.1006/pulp.1996.0042","DOIUrl":"10.1006/pulp.1996.0042","url":null,"abstract":"<div>The sensory neuropeptide, substance P (SP), is present in human airway nerves, beneath and within the epithelium where the condensed localization of neutral endopeptidase (NEP), the major enzyme degrading SP, is observed. To test the hypothesis whether SP stimulates the cough reflex and NEP modifies the cough reflex, we studied the cough response to various stimuli in awake guinea-pigs. Inhibition of NEP with phosphoramidon caused cough, which was inhibited by systemic capsaicin treatment and by aerosols of a specific NK1receptor antagonist FK 888. Aerosols of FK 888 also inhibited cough induced by bronchoconstricting agents such as acetylcholine and histamine in non-sensitized animals and by ovalbumin antigen in animals sensitized to ovalbumin. The number of coughs induced by histamine aerosols was inhibited by systemic capsaicin treatment and enhanced by pretreatment with a NEP inhibitor phosphoramidon. Likewise, FK 888 inhibited the augumented cough response to aerosolized capsaicin in female guinea-pigs treated with a long-term medication of an angiotensin-converting enzyme inhibitor, cilazapril. In humans, aerosols of SP did not cause cough in normal subjects, whereas it did in patients with common colds. The SP fragment1–9a major metabolite of SP produced by NEP, was less effective compared with SP in these patients, suggesting that damaged epithelium may facilitate the penetration of SP. These findings suggest that SP released from sensory nerves in response to stimuli may mediate cough and NEP may have a role in modulating SP-induced effects.</div>","PeriodicalId":74618,"journal":{"name":"Pulmonary pharmacology","volume":"9 5","pages":"Pages 323-328"},"PeriodicalIF":0.0,"publicationDate":"1996-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/pulp.1996.0042","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20178075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 68

The Role of Partial Laryngeal Denervation on the Cough Reflex in Awake Guinea-pigs, Rats and Rabbits 喉部分去神经支配在清醒豚鼠、大鼠和家兔咳嗽反射中的作用

Pulmonary pharmacology Pub Date : 1996-10-01 DOI: 10.1006/pulp.1996.0051

Milos Tatar, Danka Karcolova, Renata Pecova, Mariana Brozmanova

引用次数: 18

Cough: Methods and Mechanisms 咳嗽:方法与机理

Pulmonary pharmacology Pub Date : 1996-10-01 DOI: 10.1006/pulp.1996.0033

John Widdicombe

引用次数: 3

Intramural Elastase Injection Increases Responsiveness of Isolated Bronchial Segments 壁内注射弹性蛋白酶增加离体支气管段的反应性

Pulmonary pharmacology Pub Date : 1996-08-01 DOI: 10.1006/pulp.1996.0030

P.R Gray, H.W. Mitchell

{"title":"Intramural Elastase Injection Increases Responsiveness of Isolated Bronchial Segments","authors":"P.R Gray, H.W. Mitchell","doi":"10.1006/pulp.1996.0030","DOIUrl":"10.1006/pulp.1996.0030","url":null,"abstract":"<div>In cartilaginous bronchi, the smooth muscle is attached to the adventitial cartilage by a fibro-elastic matrix. In pigs, this matrix is stretched during muscle contraction so the inner airway wall reversibly uncouples from the outer wall. We hypothesized that inflammatory cell derived proteases may degrade this fibro-elastic matrix, increasing airway responsiveness. Airway responsiveness was determined from the sensitivity of perfused 2.0–3.5 mm id porcine bronchial segments to acetylcholine (ACh 10−6–10−2m) and from airway lumen narrowing imaged directly using a fibre-optic endoscope and video camera. Elastase (3μl, 1% solution) injected between the cartilage and the smooth muscle doubled sensitivity to ACh (P<0.001) in perfused segments. Maximal airway narrowing to 10−2ACh was also increased from 54% to 60% (P<0.05). Smooth muscle contraction, recorded isometrically, was not increased by elastase. We conclude that proteases may increase airway wall uncoupling in vitro, possibly by reducing the wall load, and thereby increasing responsiveness.</div>","PeriodicalId":74618,"journal":{"name":"Pulmonary pharmacology","volume":"9 4","pages":"Pages 239-243"},"PeriodicalIF":0.0,"publicationDate":"1996-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/pulp.1996.0030","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20107266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 12

Attenuation of Airway Hyperresponsiveness During Acute Viral Infection Using the 21-Aminosteroid U-83836E in Rats 21-氨基类固醇U-83836E对大鼠急性病毒感染时气道高反应性的抑制作用

Pulmonary pharmacology Pub Date : 1996-08-01 DOI: 10.1006/pulp.1996.0027

Ronald Sorkness , Robert F. Lemanske, Jr.

{"title":"Attenuation of Airway Hyperresponsiveness During Acute Viral Infection Using the 21-Aminosteroid U-83836E in Rats","authors":"Ronald Sorkness , Robert F. Lemanske, Jr.","doi":"10.1006/pulp.1996.0027","DOIUrl":"10.1006/pulp.1996.0027","url":null,"abstract":"<div>Respiratory viral infections have been associated with exacerbations of asthma in humans, and are known to produce airway obstruction and hyperresponsiveness in rats. Virus-induced airway dysfunction may result in part from inflammatory cells and their products, and agents that target these mechanisms might therefore attenuate viral airway injury. The 21-aminosteroid class of drugs has been reported to attenuate tissue injury in a variety of models, and we hypothesized that U-83836E, an orally-active aminosteroid, would prevent the development of airway dysfunction during acute viral illness. Adult rats were inoculated with either parainfluenza type 1 (Sendai) virus or sterile vehicle, treated with either U-83836E 20 mg/kg or water by oral gavage twice daily, and studied on postinoculation day 5, 6 or 7. Anesthetized, paralysed, mechanically ventilated rats were placed in a body plethysmograph for measurements of airway obstruction (resistance, dynamic compliance, eucapneic PaO2), and responsiveness to iv methacholine; lungs were lavaged to obtain inflammatory cells. The water–treated virus group was significantly different from the non-infected controls for all variables. Virus-induced hyperresponsiveness was attenuated (P=0.027) by aminosteroid treatment, although airway obstruction and inflammation were not improved by the treatment. We conclude that 21-aminosteroids may protect airways from virus-induced hyperresponsiveness.</div>","PeriodicalId":74618,"journal":{"name":"Pulmonary pharmacology","volume":"9 4","pages":"Pages 219-222"},"PeriodicalIF":0.0,"publicationDate":"1996-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/pulp.1996.0027","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20107263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 6

The Role of Cyclooxygenase and 5-Lipoxygenase Metabolites in Potentiated Endothelin-1-evoked Contractions in Bovine Bronchi 环氧合酶和5-脂氧合酶代谢物在内皮素-1诱导的牛支气管收缩中的作用

Pulmonary pharmacology Pub Date : 1996-08-01 DOI: 10.1006/pulp.1996.0026

Jane E. Nally , David C. Bunton , David Martin , Neil C. Thomson

{"title":"The Role of Cyclooxygenase and 5-Lipoxygenase Metabolites in Potentiated Endothelin-1-evoked Contractions in Bovine Bronchi","authors":"Jane E. Nally , David C. Bunton , David Martin , Neil C. Thomson","doi":"10.1006/pulp.1996.0026","DOIUrl":"10.1006/pulp.1996.0026","url":null,"abstract":"<div>We have previously shown that angiotensin II (AII) potentiates responses evoked by endothelin-1 (Et-1). In the present study, the additional ability of hypoxia or phorbol 12, 13-dibutyrate (PDBu) to evoke hyperreactivity was examined. In addition, the role of cyclooxygenase and 5-lipoxygenase metabolites of arachidonic acid in the potentiation evoked by AII, hypoxia or PDBu was studied, using indomethacin and nordihydroguaiaretic acid (NDGA). The involvement of protein kinase C in the enhanced response was examined using staurosporine. Contractions were measured isometrically from rings of bovine bronchi. Contractions evoked by Et-1 alone were unaltered by indomethacin (10−6m), NDGA (10−5m) or staurosporine (3×10−8m). AII (3×10−7m), hypoxia (4% O2) or PDBu (10−8m) each significantly potentiated the contractions evoked by Et-1. Indomethacin (10−6m) virtually abolished the effect of AII, hypoxia or PDBu. NDGA (10−5m) reversed the potentiating effect of both AII and hypoxia and partially reversed PDBu-evoked enhancement of Et-1-mediated responses. Staurosporine (3×10−8m) abolished the ability of AII or PDBu, but not hypoxia, to enhance Et-1-mediated contractions. In conclusion, AII, hypoxia and PDBu evoke hyperresponsiveness which is mediated by prostanoids and/or leukotrienes, the precise nature of which remains to be elucidated. Differences in the ability of staurosporine to reverse AII- and hypoxia-induced hyperreactivity suggests, however, that these conditions may generate different eicosanoids.</div>","PeriodicalId":74618,"journal":{"name":"Pulmonary pharmacology","volume":"9 4","pages":"Pages 211-217"},"PeriodicalIF":0.0,"publicationDate":"1996-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/pulp.1996.0026","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20107262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 8

The Effect of Bacterial Toxins on Levels of Intracellular Adenosine Nucleotides and Human Ciliary Beat Frequency 细菌毒素对细胞内腺苷核苷酸水平和人纤毛搏动频率的影响

Pulmonary pharmacology Pub Date : 1996-08-01 DOI: 10.1006/pulp.1996.0028

K. Kanthakumar , G.W. Taylor , D.R. Cundell , R.B. Dowling , M. Johnson , P.J. Cole , R. Wilson

{"title":"The Effect of Bacterial Toxins on Levels of Intracellular Adenosine Nucleotides and Human Ciliary Beat Frequency","authors":"K. Kanthakumar , G.W. Taylor , D.R. Cundell , R.B. Dowling , M. Johnson , P.J. Cole , R. Wilson","doi":"10.1006/pulp.1996.0028","DOIUrl":"10.1006/pulp.1996.0028","url":null,"abstract":"<div>Toxins that slow ciliary beat are virulence determinants of bacteria that infect or invade ciliated epithelial surfaces. We have previously shown that the effect of thePseudomonas aeruginosatoxin pyocyanin on ciliary beat is associated with a fall in intracellular cAMP and ATP. We have now investigated whether reduction in intracellular adenosine nucleotides might be a common mechanism of action of other bacterial toxins which slow ciliary beat. Two otherP. aeruginosatoxins, 1-hydroxyphenazine (1-HP) and rhamnolipid, and twoHaemophilus influenzaefractions produced by gel filtration of broth cultures were tested. The effect on human nasal epithelium ciliary beat frequency (CBF), and intracellular cAMP and ATP were measured, and the effect of two pharmacological agents, dibutyryl cAMP and salmeterol, on these changes was assessed. 1-HP, rhamnolipid and the twoH. influenzaefractions slowed CBF before there was significant release of lactate dehydrogenase from the cells. The toxins also caused a fall in intracellular cAMP and ATP. Dibutyryl cAMP and salmeterol at the concentrations used do not increase baseline CBF, but diminished the fall in CBF and intracellular adenosine nucleotides. The cAMP and ATP levels in these studies were combined with those previously obtained with pyocyanin. There was a good correlation between cAMP and ATP levels and CBF. Bacterial toxins which slow CBF may act by causing a fall in intracellular adenosine nucleotides, and agents which stimulate cAMP may prevent toxin-induced slowing of ciliary beat.</div>","PeriodicalId":74618,"journal":{"name":"Pulmonary pharmacology","volume":"9 4","pages":"Pages 223-230"},"PeriodicalIF":0.0,"publicationDate":"1996-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/pulp.1996.0028","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20107264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 34

Pulmonary Protective and Vasodilator Effects of a StandardizedPanax GinsengPreparation Following Artificial Gastric Digestion 标准人参制剂对人工胃消化后肺保护和血管扩张的作用

Pulmonary pharmacology Pub Date : 1996-08-01 DOI: 10.1006/pulp.1996.0025

S. Rimar , M. Lee-Mengel , C.N. Gillis

{"title":"Pulmonary Protective and Vasodilator Effects of a StandardizedPanax GinsengPreparation Following Artificial Gastric Digestion","authors":"S. Rimar , M. Lee-Mengel , C.N. Gillis","doi":"10.1006/pulp.1996.0025","DOIUrl":"10.1006/pulp.1996.0025","url":null,"abstract":"<div>We have previously demonstrated that purified ginsenosides produce pulmonary vasodilation and prevent effects of free radical injury on the lung. We examined the effect of artificially digested standardized ginseng preparation G115 in perfused rabbit lungs. G115 was incubated in artificial gastric juice (0.03 M NaCl+0.08 M HCl) 37°C for 1 h, and artificial intestinal juice (0.05 M KH2PO4+0.02 M NaOH) 37°C for 5 h, neutralized with NaOH and lyophilized. Pulmonary vasoconstriction was induced with U46619, and cumulative additions of G115 in undigested, gastric digested and gastric and intestinal digested forms were made to the perfusate. In separate experiments, oxygen free radical injury by electrolysis was produced in the presence of G115 in the perfusate and ACh-induced vasodilation assessed before and after injury. Undigested, gastric digested and combined gastric and intestinal digested G115 significantly dilated lungs (44%, undigested; 26%, gastric digested; 45%, gastric and intestinal digested). In addition, both undigested (−27±5% vs. −24±5%) as well as gastric and intestinal digested G115 (−23±3% vs. −16±2%) preserved ACh-induced vasodilation following injury. Artificially digested G115 is a pulmonary vasodilator which protects against free radical injury, suggesting that oral G115 has the same effects.</div>","PeriodicalId":74618,"journal":{"name":"Pulmonary pharmacology","volume":"9 4","pages":"Pages 205-209"},"PeriodicalIF":0.0,"publicationDate":"1996-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/pulp.1996.0025","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20107261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 31

Effect of Leukotriene D4 on Ciliary Activity in Human, Guinea-Pig and Rat Respiratory Mucosa 白三烯D4对人、豚鼠和大鼠呼吸道黏膜纤毛活性的影响

Pulmonary pharmacology Pub Date : 1996-08-01 DOI: 10.1006/pulp.1996.0029

Susanna Joki , Veijo Saano , Tommi Koskela , Elina Toskala , Michael A. Bray , Juhani Nuutinen

{"title":"Effect of Leukotriene D4 on Ciliary Activity in Human, Guinea-Pig and Rat Respiratory Mucosa","authors":"Susanna Joki , Veijo Saano , Tommi Koskela , Elina Toskala , Michael A. Bray , Juhani Nuutinen","doi":"10.1006/pulp.1996.0029","DOIUrl":"10.1006/pulp.1996.0029","url":null,"abstract":"<div>Leukotriene D4 (LTD4) is a potent bronchoconstrictor and inflammatory mediator in asthma. Data concerning the effects of LTD4 on ciliary function in the respiratory tract are sparse and contradictory. The purpose of the present study was to clarify the effects of LTD4 on mucociliary activity using the tracheal mucosa of two laboratory animal species, guinea-pig and rat, as well as human nasal mucosa. The ciliary beat frequency (CBF) was measured photoelectrically and determined by Fast Fourier Transform computer analysis. Additionally the structure of ciliated epithelia of guinea-pig trachea after LTD4-immersion was investigated using a scanning electron microscope (SEM). In all tissues, LTD4 increased CBF showing a bell-shaped dose–response curve. The maximum effect was 75±30% in guinea-pig at 10−9mol/l, 119±49% in rat at 10−7mol/l, and 86±28% at 10−6mol/l in human tissue. In guinea-pig tracheal mucosa, there was an indication of an increase in the amount of mucus and disorientation of cilia were seen by SEM after immersion in LTD4. These findings suggest that LTD4 stimulates ciliary activity, but impairs the orientation of cilia.</div>","PeriodicalId":74618,"journal":{"name":"Pulmonary pharmacology","volume":"9 4","pages":"Pages 231-238"},"PeriodicalIF":0.0,"publicationDate":"1996-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/pulp.1996.0029","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20107265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 15