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At least 631 records · Page 35Linked to original sources
PubMed1994

Mechanism of pacemaker induced cough.

Single chamber ventricular pacing (VVI) may be associated with a group of adverse symptoms known as the pacemaker syndrome. Cough is an unusual but recognised feature of the pacemaker syndrome. A patient with a VVI permanent pacemaker experienced a disturbing cough during VVI pacing. There were no other symptoms associated with the pacemaker syndrome. The effects of short-term ventricular pacing on the cough were examined while the subject was standing and lying. After control recordings, the pulse generator was programmed to either VVI 50 beats/min or 90 beats/min and recordings made over 60 seconds. There was an interval of 60s between recordings. Overall, five recording periods at VVI of 50 beats/min and VVI of 90 beats/min were made in random order. The patient was blinded to the order of programming. The recordings were repeated with the subject lying. Cough was not found during normal sinus rhythm. During VVI pacing the patient experienced a tickling sensation in the throat associated with intermittent coughing. The number of coughs decreased during each successive recording period. The pacing cough reflex was enhanced when the patient was lying down. The mechanism of cough during VVI pacing is uncertain. The findings suggest a possible role for afferent vagal receptors from the airways.

Cough↗
PubMed2000

Capsaicin induced cough in cryptogenic fibrosing alveolitis.

BACKGROUND: Cough is a common and troublesome symptom in cryptogenic fibrosing alveolitis (CFA) but the mechanisms responsible are not known. The cough threshold to inhaled capsaicin is increased in asthma and chronic obstructive pulmonary disease (COPD) where lung volumes are increased, but the relationship between cough response and symptom intensity has not been studied in CFA where lung volumes are reduced. METHODS: Capsaicin challenge tests were performed on 15 subjects with proven CFA and 96 healthy controls. Symptoms, as assessed by daily diary card cough score and by visual analogue scale (VAS), were related to the capsaicin sensitivity (C5) and compared with lung volumes. Volume restriction was produced in a group of 12 normal healthy subjects by a plastic shell tightly strapped to the chest wall. Capsaicin challenge tests were performed in these subjects, both strapped and unstrapped, to determine whether volume restriction altered the cough reflex. RESULTS: The median C5 response in normal subjects was more than 500 microM compared with 15.6 microM in those with CFA (p<0.001). The C5 response of the CFA patients was not related to symptoms of cough (whether measured by diary card or by VAS), nor was it related to percentage predicted total lung capacity (TLC) or forced vital capacity (FVC). Volume restriction of normal subjects with chest strapping successfully restricted lung volumes to levels similar to that of the CFA patients but did not change the sensitivity to capsaicin. CONCLUSIONS: The cough reflex measured using capsaicin is markedly increased in patients with CFA. This increase is not the result of alterations in the deposition of inhaled particles of capsaicin brought about by volume restriction. It could be related to reduced lung compliance leading to sensitisation of rapidly adapting receptors, other mechanical changes, or to destruction of pulmonary C fibres secondary to interstitial inflammation. The capsaicin test may be a useful method of objectively monitoring cough propensity in CFA.

Adult↗
PubMed2003

Impaired cough reflex in patients with recurrent pneumonia.

BACKGROUND: A substantial proportion of patients with recurrent pneumonia do not have an apparent underlying condition, but they may have unknown defects in host defence mechanisms such as cough reflex. METHODS: Capsaicin cough sensitivity was measured in seven patients with recurrent pneumonia but no underlying condition. Recurrent pneumonia was defined as at least two episodes of pneumonia in 1 year, or three or more episodes at any time. After remission of pneumonia, 10 doubling concentrations of capsaicin (1.22-625 microM) were inhaled until five or more coughs were induced (cough threshold). Mucociliary clearance was assessed on the basis of nasal ciliary beat frequency and nasal clearance time. Twenty one age and sex matched healthy subjects were studied as controls. RESULTS: Each patient had 2-6 episodes of pneumonia. Most episodes developed in dependent lung segments, suggesting the involvement of silent aspiration. Log transformed cough threshold was significantly higher in patients than in controls (mean 2.37 M (95% CI 1.84 to 2.90) v 1.29 microM (95% CI 1.11 to 1.47); p<0.0001). The effect of pneumonia per se on cough reflex seemed unlikely since the cough threshold showed little change when re-examined after 3 months. The patients and controls did not differ with respect to the indices of mucociliary clearance. CONCLUSIONS: Impaired cough reflex may be involved in the pathogenesis of recurrent pneumonia.

Adult↗
PubMed1984

Coughs cause systemic blood flow.

Although it is known that rhythmic coughing can preserve consciousness during ventricular fibrillation, the arterial pressure transients which result have not yet been shown to reflect forward blood flow in man. The effectiveness of cough in causing forward flow in eight normal volunteers with bradycardia was studied. They coughed between cardiac cycles, using an audio and visual display of the electrocardiogram. The force of the cough was varied and measured with an oesophageal balloon. Blood flow was recorded with a Döppler velocity probe over the radial artery and a finger or ear photoplethysmograph. Motion artefact on the Döppler record due to coughing was excluded by transiently obstructing the brachial artery. We compared the areas under 5-10 consecutive Döppler and photoplethysmograph pulse flow tracings due to the cough and heart beat with those due to the immediately preceding heart beat alone. They were significantly increased. This augmentation was greater in those flow pulses accompanied by a more vigorous cough. It is concluded that coughing is associated with an effort dependent forward flow pulse in the arterial circulation.

Adult↗
PubMed1992

Effects of methacholine induced bronchoconstriction and procaterol induced bronchodilation on cough receptor sensitivity to inhaled capsaicin and tartaric acid.

BACKGROUND: The direct effect of bronchoconstriction on cough receptor sensitivity is unknown, and the antitussive effect of beta 2 adrenergic agonists in man has been controversial. This study was designed to throw light on these questions. METHODS: The threshold of the cough response to inhaled capsaicin, a stimulant acting on C fibre endings, and tartaric acid, a chemostimulant, was measured before and 10 minutes after inhalation of methacholine, which caused a nearly 20% fall in forced expiratory volume in one second (FEV1), in 14 normal subjects (study 1), and also before and 30 minutes after inhalation of procaterol (30 micrograms), placebo, and saline in eight normal subjects (study 2). Progressively increasing concentrations of capsaicin and tartaric acid solutions were inhaled for 15 seconds by mouth tidal breathing at one minute intervals and cough threshold was defined as the lowest concentration of capsaicin and tartaric acid that elicited five or more coughs. RESULTS: In study 1 the geometric mean values of the cough threshold of response to capsaicin and tartaric acid before methacholine callenge, 2.98 (GSE 1.30) micrograms/ml and 46.6 (1.22) mg/ml, were not significantly different from those of the response to methacholine inhalation, 3.45 (1.33) micrograms/ml and 32.9 (1.37) mg/ml. In study 2 the geometric mean value of the cough threshold of response to capsaicin before inhalation of procaterol (4.61 (GSE 1.84) micrograms/ml) was not different from that after inhalation of procaterol (4.61 (GSE 1.84) micrograms/ml), which had significant bronchodilator effects. The cough threshold was not altered by placebo or saline. CONCLUSIONS: These findings suggest that muscarinic receptor stimulation, bronchoconstriction, beta 2 receptor stimulation, or bronchodilation might have no direct effect on the sensitivity of the cough receptors in normal subjects.

Adult↗
PubMed1997

Human ACE gene polymorphism and distilled water induced cough.

BACKGROUND: Inhibitors of angiotensin converting enzyme (ACE) cause a non-productive cough. The insertion/deletion polymorphism of ACE was used as a genetic marker to investigate the relationship between ACE genotype and cough sensitivity. METHODS: A double blind cough challenge was performed in 66 normotensive subjects (34 men) of mean age 34.8 years (range 18-80) using aerosols of distilled water. The number of coughs during the one minute exposure to water was recorded. DNA samples from venous blood were amplified by the polymerase chain reaction and resolved on a 1% agarose gel. They were analysed for the presence of a polymorphism in intron 16 of the ACE gene consisting of an insertion (I) or deletion (D) of an Alu repetitive sequence 287 base pairs long. RESULTS: The distribution of genotypes was 20 II, 26 ID, and 20 DD. The cough response was significantly (p < 0.01) related to the ACE genotype, the mean number of coughs being 15.8, 11.3, and 9.6, respectively, in subjects with the II, ID, and DD genotypes. CONCLUSIONS: The observation that cough challenge is dependent on ACE genotype in normal subjects is evidence of a link between ACE activity and the cough reflex.

Adolescent↗
PubMed1998

Gastro-oesophageal reflux related cough and its response to laparoscopic fundoplication.

BACKGROUND: This study was designed to determine prospectively the rate of cough before and after laparoscopic Nissen fundoplication performed for the control of gastro-oesophageal reflux disease. METHODS: One hundred and ninety five consecutive patients (76 men) of mean (SD) age 46.9 (14.1) years with proven gastro-oesophageal reflux disease, who were either on long term omeprazole (n = 187) or who had not responded to a trial of omeprazole (n = 8), took part in the study which was carried out in a university teaching hospital that included a regional respiratory referral centre. Patients underwent oesophageal manometry, 24 hour oesophageal pH testing, and symptom score evaluation by an independent observer before and six months after laparoscopic Nissen fundoplication. RESULTS: One hundred and thirty three patients presented with reflux symptoms and 62 with respiratory symptoms; 68% of patients complained of cough before surgery (86% with respiratory symptoms, 60% with gastrointestinal symptoms). The percentage reflux time in 24 hours fell significantly (p < 0.0001) from a mean (SD) of 9.38 (10.99)% to 1.22 (2.92)%, lower oesophageal sphincter tone rose significantly (p < 0.0001) from a mean (SD) of 7.71 (5.90) mm Hg to 21.74 (10.84) mm Hg, and the cough score fell from a median value of 8.0 (IQR 12.0) to 0 (IQR 3) following surgery. Of the patients with cough, 51% were cough free after surgery and 31% improved. The patients with respiratory symptoms had a higher cough score before (median 12.0 (IQR 5.5) versus 4.0 (IQR 8.75), p < 0.0001) and after surgery (median 1 (7.5) versus 0.0 (IQR 1.0), p = 0.0045) than those with gastrointestinal symptoms. CONCLUSIONS: Patients who present to gastroenterologists with severe reflux commonly complain of cough. Laparoscopic Nissen fundoplication is effective in the control of cough in patients with gastro-oesophageal reflux disease, with or without primary respiratory disease.

Adolescent↗
PubMed1999

Cough threshold in patients with chronic obstructive pulmonary disease.

BACKGROUND: Cough is an important symptom of patients with chronic obstructive pulmonary disease (COPD). The cough threshold to citric acid and capsaicin in patients with COPD and in normal volunteers was measured, as well as bronchial hyperresponsiveness to methacholine. METHODS: Nineteen patients with COPD and 22 controls were recruited. Subjects underwent a methacholine bronchoprovocation test and a cough challenge to citric acid and capsaicin. RESULTS: The log citric acid cough threshold D2 (concentration causing two coughs) was significantly lower in patients with COPD (mean 2.17 versus 2.56, mean difference (95% CI) 0.39 (0.04 to 0.74), p = 0.02) but not for capsaicin cough D2 (0.66 versus 0.8, p = 0.41). Sixteen patients with COPD had bronchial hyperresponsiveness which was correlated with baseline FEV1 (r = 0.6, p = 0.01, 95% CI 0.15 to 0.84). CONCLUSIONS: Patients with COPD have a lower cough threshold to citric acid, possibly due to a differential effect of cigarette smoke on citric acid sensitive cough receptors.

Adult↗
PubMed2006

Mechanistic studies of acid-evoked coughing in anesthetized guinea pigs.

Experiments carried out in conscious guinea pigs suggest that citric acid-evoked coughing is partly mediated by transient receptor potential vanilloid type 1 (TRPV1) receptor-dependent activation of tachykinin-containing, capsaicin-sensitive C fibers. In vitro electrophysiological analyses indicate, however, that acid also activates capsaicin-sensitive and -insensitive vagal afferent nerves by a TRPV1-independent mechanism, and studies in anesthetized guinea pigs show that coughing evoked by acid is mediated by activation of capsaicin-insensitive vagal afferent nerves. In the present study, we have characterized the mechanisms of citric acid-evoked coughing in anesthetized guinea pigs. Drugs were administered directly to the Krebs buffer perfusing the extrathoracic trachea. Citric acid was applied topically to the tracheal mucosa, directly into the tracheal perfusate in increasing concentrations and at 1-min intervals. Citric acid dose dependently evoked coughing in anesthetized guinea pigs. This was mimicked by hydrochloric acid but not by sodium citrate. The coughing evoked by acid was nearly or completely abolished by TTX or by cutting the recurrent laryngeal nerves. Perfusing the trachea with a low Cl- buffer potentiated the acid-induced cough reflex. In contrast, prior capsaicin desensitization, 10 microM capsazepine, Ca2+-free perfusate, 0.1 microM iberiotoxin, 1 microM atropine, 10 microM isoproterenol, 10 microM albuterol, 3 microM indomethacin, 0.1 microM HOE-140, a combination of neurokinin1 (NK1; CP-99994), NK2 (SR-48968), and NK3 (SB-223412) receptor antagonists (0.1 microM each), a combination of histamine H1 (3 microM pyrilamine) and cysLT1 (1 microM ICI-198615) receptor antagonists, superior laryngeal nerve transection, or epithelium removal did not inhibit citric acid-evoked coughing. These and other data indicate that citric acid-evoked coughing in anesthetized guinea pigs is mediated by direct activation of capsaicin-insensitive vagal afferent nerves, perhaps through sequential activation of acid-sensing ion channels and chloride channels.

Anesthesia↗
PubMed1981

Cough dynamics during progressive expiratory muscle weakness in healthy curarized subjects.

The dynamics of voluntary cough were studied in healthy supine subjects during four successive infusions of d-tubocurarine (dTc) (0.05 mg/kg) to assess the effects of progressive expiratory muscle weakness on cough performance. Curarization produced a progressive decline in maximal static expiratory muscle strength (PEmax) measured at the mouth and in pleural pressures (Ppl) generated during coughing. Expiratory flow rates during coughing did not decrease except during the initial cough from total lung capacity with the last dTc dose (18% below control). This was associated with a decrease in end-inspiratory volume prior to coughing and with a marked decrease in Ppl to 30% of control. Although the decrease in flow rates was minimal compared with Ppl, flow patterns suggest that dynamic airway compression was reduced during these coughs. We conclude that the principal effect of the expiratory muscle weakness in curarized subjects is to reduce the cough-induced dynamic compression and linear velocity of airflow though the major intrathoracic airways.

Adult↗
PubMed1989

Role of costal and crural diaphragm and parasternal intercostals during coughing in cats.

The inspiratory phase of coughs often consists of large inspired volumes and increased motor discharge to the costal diaphragm. Furthermore, diaphragm electrical activity may persist into the early expiratory portion of coughs. To examine the role of other inspiratory muscles during coughing, electromyograms (EMG) recorded from the crural diaphragm (Dcr) and parasternal intercostal (PSIC) muscles were compared to EMG of the costal diaphragm (Dco) in anesthetized cats. Tracheal or laryngeal stimulation typically produced a series of coughs, with variable increases in peak inspiratory EMGs of all three muscles. On average, peak inspiratory EMG of Dco increased to 346 +/- 60% of control (P less than 0.001), Dcr to 514 +/- 82% of control (P less than 0.0002), and PSIC to 574 +/- 61% of control (P less than 0.0005). Augmentations of Dcr and PSIC EMG were both significantly greater than of Dco EMG (P less than 0.05 and P less than 0.002, respectively). In most animals, EMG of Dco correlated significantly with EMG of Dcr and of PSIC during different size coughs. Electrical activity of all three muscles persisted into the expiratory portions of many (but not all) coughs. The duration of expiratory activity lasted on average 0.17 +/- 0.03 s for Dco, 0.25 +/- 0.06 s for Dcr, and 0.31 +/- 0.09 s for PSIC. These results suggest that multiple respiratory muscles are recruited during inspiration of coughs, and that the persistence of electrical activity into expiration of coughs is not unique to the costal diaphragm.

Animals↗
PubMed1998

Effects of airway inflammation on cough response in the guinea pig.

We have developed a guinea pig model for cough related to allergic airway inflammation. Unanesthetized animals were exposed to capsaicin aerosols for 10 min, and cough frequency was counted during this period. The cough evaluation was performed by the following three methods: visual observation, acoustic analysis, and monitoring of pressure changes in the body chamber. These analyses clearly differentiated a cough from a sneeze. To elucidate the relationship between cough response and airway inflammation, animals were immunosensitized and multiple challenged. Sensitized guinea pigs presented no specific changes microscopically, but multiple-challenged animals showed an increased infiltration of inflammatory cells into the airway. Cough number in response to capsaicin increased significantly from 4.7 +/- 1.4 coughs/10 min in normal animals to 10.6 +/- 2.0 coughs/10 min in sensitized animals and further to 22.8 +/- 1.3 coughs/10 min in multiple-challenged animals. This augmented cough frequency was significantly inhibited by the inhalation of tachykinin-receptor antagonists and by oral ingestion, but not inhalation, of codeine phosphate. The results suggest that airway inflammation potentiates an elevation of cough sensitivity in this model.

Animals↗
PubMed2000

Volume-timing relationships during cough and resistive loading in the cat.

The relationship between pulmonary volume-related feedback and inspiratory (CTI) and expiratory (CTE) phase durations during cough was determined. Cough was produced in anesthetized cats by mechanical stimulation of the intrathoracic tracheal lumen. During eupnea, the animals were exposed to single-breath inspiratory and expiratory resistive loads. Cough was associated with large increases in inspiratory volume (VI) and expiratory volume (VE) but no change in phase durations compared with eupnea. There was no relationship between VI and CTI during coughing. A linear relationship with a negative slope existed between VI and eupneic inspiratory time during control and inspiratory resistive loading trials. There was no relationship between VE and CTE during all coughs. However, when the first cough in a series or a single cough was analyzed, the VE/CTE relationship had a positive slope. A linear relationship with a negative slope existed between VE and eupneic expiratory time during control and expiratory resistive loading trials. These results support separate ventilatory pattern regulation during cough that does not include modulation of phase durations by pulmonary volume-related feedback.

Airway Resistance↗
PubMed2001

Ethnic and gender differences in cough reflex sensitivity.

BACKGROUND: Although recent studies have suggested that the cough reflex is more sensitive in women than in men, ethnic differences in cough reflex sensitivity have not previously been investigated. OBJECTIVES: To evaluate ethnic and gender differences in cough reflex sensitivity. METHODS: We performed capsaicin cough challenge testing in 182 healthy volunteers of three distinct ethnic groups: Caucasian (white, non-Hispanic, of European origin), Indian (originating from the Indian subcontinent) and Chinese. The concentration of capsaicin inducing 2 or more (C2) and 5 or more coughs (C5) was determined in each subject. RESULTS: Mean (+/-SEM) values for log C5 demonstrated that, within each ethnic group, the cough reflex was more sensitive in women: p = 0.00002 for Caucasian subjects; p = 0.003 for Indian volunteers; and p = 0.002 for Chinese subjects. Examination of C2 data yielded similar results. When subjects were evaluated by gender, multivariate analysis of variance demonstrated no ethnic differences in sensitivity to capsaicin. CONCLUSION: Our data do not support the presence of significant ethnic differences in cough reflex sensitivity, but do confirm previous data demonstrating lower cough thresholds in women.

Administration, Inhalation↗
PubMed2000

Bradykinin B(2) receptor gene polymorphism is associated with angiotensin-converting enzyme inhibitor-related cough.

The appearance of cough in association with angiotensin-converting enzyme (ACE) inhibitors is thought to be related to bradykinin, and it has been speculated that the elicitation of adverse effects is genetically predetermined. Several polymorphisms of the human bradykinin B(2) receptor gene may be involved in ACE inhibitor-related cough. To investigate this possibility, we identified the -58 thymine (T)/cytosine (C) polymorphism in subjects with ACE inhibitor-related cough. We classified the study population into 4 groups: subjects with and without cough that were treated with ACE inhibitors (n=30/30), nontreated essential hypertensive subjects (n=100), and normotensive subjects (n=100). The -58T/C was genotyped by the polymerase chain reaction single-strand conformation polymorphism method. The frequencies of the CC genotype and C allele of -58T/C were significantly higher in the nontreated hypertensive subjects than in the normotensive subjects. Conversely, the frequencies of the TT genotype and T allele were significantly higher in the subjects with cough than in the subjects without cough. These tendencies were more pronounced in females. Among the promoter assays of the human bradykinin B(2) receptor, -58T was found to have a higher transcription rate than that of -58C. This finding seems to suggest that the transcriptional activity of promoter might be involved in the appearance of ACE inhibitor-related cough. A genetic variant of the bradykinin receptor is involved in the elicitation of ACE inhibitor-related cough. It may be possible to predict the side effects of ACE inhibitors in advance.

Adult↗
PubMed1994

Pathogenesis of chronic persistent cough associated with gastroesophageal reflux.

It was previously shown that unexplained chronic cough is associated with asymptomatic gastroesophageal reflux. The aim of this study was to determine if distal esophageal acid is important in the pathogenesis of this cough. In 22 patients with cough and reflux as determined by 24-h ambulatory esophageal pH monitoring, distal esophageal acid perfusion was performed in a double-blind controlled fashion. Patients received both 0.1 N HCl and 0.9% saline for 15 min, in random order. Cough was recorded with a microphone and then computer analyzed. In 12 matched control subjects, 24-h ambulatory esophageal pH monitoring and distal esophageal acid perfusion studies were also performed. In patients, there was a significant increase in cough frequency, median (range): 36.5 (6 to 111) versus 8.3 (0 to 46)/15 min, p < 0.001, and amplitude, geometric mean (range): 85.2 (78.1 to 92.3) versus 73.1 (0.0 to 87.1) dB, p < 0.01, with HCl compared with saline. During HCl infusion, compared with control subjects, patients had more cough episodes, 36.5 (6 to 111) versus 0.0 (0 to 11)/15 min, p < 0.0001, with greater amplitude, 85.2 (78.1 to 92.3) versus 0.0 (0.0 to 79.6) dB, p < 0.001, but there was no difference in cough duration. We subsequently investigated whether inhibition of the induced cough was possible. In seven patients repeat esophageal acid perfusion was performed 15 min after the esophageal instillation of 4 ml of 4% lignocaine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Role of substance P in cough during bronchoconstriction in awake guinea pigs.

To examine the role of substance P (SP) in cough during bronchoconstriction, we studied the effects of an aerosolized beta-adrenoceptor agonist, procaterol, and a specific inhibitor of SP (NK1) receptor, FK 888, on bronchoconstriction and cough induced by aerosols of histamine and acetylcholine (ACh) in unsensitized guinea pigs and by those of ovalbumin (OA) antigen in guinea pigs sensitized to OA. Intensity of bronchoconstriction was evaluated by the time to onset of bronchoconstriction after the inhalation of bronchoconstrictors. Both procaterol (10(-6) to 10(-4) M, 2 min) and FK 888 (10(-7) to 10(-5) M, 2 min) dose dependently decreased the number of coughs and increased the time to onset of bronchoconstriction induced by histamine (10(-2) M, 15 s). Procaterol attenuated histamine-induced cough only at the concentrations effective to inhibit bronchoconstriction. However, FK 888 at concentrations of 10(-7) and 10(-6) M decreased the number of coughs without effect on bronchoconstriction. Likewise, the inhibitory effects of procaterol (10(-5) M, 2 min) on the number of coughs were parallel to those on bronchoconstriction induced by ACh (10(-1) M, 15 s) and OA antigen (0.1% concentration, 30 s), but FK 888 (10(-6) M, 2 min) decreased the number of coughs without effect on bronchoconstriction induced by them. The number of coughs induced by histamine (10(-2) M, 15 s) was inhibited by systemic capsaicin treatment and enhanced by phosphoramidon (10(-5) M, 5 min) without effect on bronchoconstriction. (ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1996

Angiotensin-converting enzyme inhibitor and danazol increase sensitivity of cough reflex in female guinea pigs.

To examine the mechanisms of an angiotensin-converting enzyme (ACE) inhibitor-induced cough in perimenopausal and postmenopausal women, cough responses to aerosols of capsaicin and citric acid were examined in four groups of female guinea pigs treated orally with danazol (D) (an agent decreasing plasma estrogen levels), cilazapril (C) (an inhibitor of ACE), both danazol and cilazapril (C+D), or without either drug (control group) for 4 to 5 wk. Capsaicin caused dose-dependent increases in the number of coughs in all four groups. C or D alone shifted dose-response curves to capsaicin (from 10(-7) M to 10(-3) M) to lower concentrations compared with the control, and C+D further shifted them. Likewise, the number of coughs induced by citric acid (3 x 10(-1) M; 2 min) was highest in animals treated with C+D and significantly higher in animals treated with C or D than in the control group. Aerosols of a selective substance P (SP) receptor antagonist FK 888 (10(-5) M; 2 min) inhibited capsaicin-induced cough in all four groups, and dose-response curves to capsaicin did not differ significantly at any concentrations among the four groups in the presence of FK 888 (p > 0.10). D decreased cyclic AMP levels in the trachea, irrespective of the combination of C. A beta 2-adrenoceptor agonist, procaterol, which is thought to inhibit SP release by elevation of cyclic AMP in sensory nerves, dose-dependently inhibited the number of coughs induced by capsaicin (10(-3) M) in animals treated with D. The present study suggests that SP is a common mechanism mediating increases in the sensitivity of cough reflex induced by both ACE inhibition and a decrease in plasma estrogen levels, and the additive effects of the two events may explain the high incidence of cough during ACE inhibitor therapy in perimenopausal and postmenopausal women.

Adrenergic beta-Agonists↗