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See detailRole of bradykinin and tachykinins in the potentiation by enalapril of coughing induced by citric acid in pigs.
Moreaux, B.; Advenier, C.; Gustin, Pascal ULg

in Fundamental & Clinical Pharmacology (2001), 15(1), 23-29

Angiotensin-converting enzyme (ACE) inhibitors are among the first-choice drugs for treating hypertension and congestive heart disease. It has been reported, however, that these drugs could induce chronic ... [more ▼]

Angiotensin-converting enzyme (ACE) inhibitors are among the first-choice drugs for treating hypertension and congestive heart disease. It has been reported, however, that these drugs could induce chronic cough and airway hyperresponsiveness. The aim of this work was to assess in pigs the effects of bradykinin and tachykinins on citric-acid-induced coughing after ACE inhibitor pretreatment. Coughing was induced by challenging pigs with an aerosol of 0.8 M citric acid over 15 min. Coughs were counted by a trained observer for 30 min. The animals underwent two cough induction tests two days apart (days 1 and 3), the first being taken as a control. All drugs were injected intravenously 30 min before the second challenge. In the control group, no difference was observed between days 1 and 3. The ACE inhibitor enalapril (7.5 and 15 microg/kg) caused the cough frequency to increase significantly. In contrast, a dose-related decrease was observed with Hoe140 (icatibant), a bradykinin B2 receptor antagonist (0.5 and 1 mg/kg). When both drugs were administered simultaneously (15 microg/kg for enalapril and 1 mg/kg for Hoe140), a significant increase was observed as compared with the control value obtained on day 1. When enalapril was combined with the three tachykinin receptor antagonists SR 140333 (NK1 receptor antagonist), SR 48968 (NK2 receptor antagonist) and SR 142801 (NK3 receptor antagonist), a significant decrease was observed as compared with control value obtained on day 1; the percentage of variation was also significantly different as compared with those observed in enalapril groups at both doses. These data suggest that ACE-inhibitor-induced enhancement of the cough reflex is mainly due to tachykinins and not to bradykinin in our pig model. Bradykinin, however, plays a major role in coughing induced by citric acid alone. [less ▲]

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See detailRole of Substance P and Tachykinin Receptor Antagonists in Citric Acid-Induced Cough in Pigs
Moreaux, B.; Nemmar, A.; Vincke, G. et al

in European Journal of Pharmacology (2000), 408(3), 305-312

The purpose of this work was to investigate the role of tachykinins in cough induced by citric acid (0.8 M) in pigs. With this object, we have studied the effect of citric acid on substance P content in ... [more ▼]

The purpose of this work was to investigate the role of tachykinins in cough induced by citric acid (0.8 M) in pigs. With this object, we have studied the effect of citric acid on substance P content in the tracheo-bronchial tree and the effects of substance P and of tachykinin receptor antagonists on citric acid-induced cough. Citric acid exposure significantly increased substance P concentration in both broncho-alveolar and tracheal lavage fluids, while it decreased significantly the substance P content in tracheal mucosa. Substance P did not elicit cough, but significantly potentiated the citric acid-induced cough frequency. Tachykinin NK(1), NK(2) or NK(3) receptor antagonists, SR 140333 (nolpitantium), SR 48968 (saredutant) and SR 142801 (osanetant), respectively, significantly inhibited citric acid-induced cough. The same inhibitory effect of tachykinin receptor antagonists was observed, when substance P was nebulised before citric acid challenge. We conclude that citric acid induces in pigs a release of substance P in the tracheo-bronchial tree, which plays a sensitising role on the cough reflex. The involvement of tachykinin NK(1), NK(2), NK(3) receptors are also demonstrated in this reflex. [less ▲]

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See detailInhibiting Effect of Ammonia on Citric Acid-Induced Cough in Pigs: A Possible Involvement of Substance P
Moreaux, B.; Nemmar, A.; Beerens, Dominique ULg et al

in Pharmacology & Toxicology (2000), 87(6), 279-285

The effect of ammonia on the cough response to citric acid and on substance P release from C-fibers involved in this reflex was assessed. For a period from one to four days, piglets were exposed, in an ... [more ▼]

The effect of ammonia on the cough response to citric acid and on substance P release from C-fibers involved in this reflex was assessed. For a period from one to four days, piglets were exposed, in an inhalation chamber, to ammonia at a concentration of 15 or 30 ppm. During exposure, cough induction tests were done every two days. Recovery of the cough reflex after ammonia exposure was also determined. In a separate group of piglets exposed for 2 days to 30 ppm ammonia, substance P content was determined in bronchial and tracheal lavage fluids and in the tracheal and bronchial mucosa. Ammonia (30 ppm) was found to inhibit coughing significantly (the cough frequency was reduced by 64%) after a two-day exposure. In animals exposed for 4 days to this ammonia concentration, the recovery ranged from 3 to 7 days (mean: 5 days). The same ammonia concentration also caused the substance P content to increase significantly in bronchoalveolar lavage fluid (to 432% of its initial value) and tracheal lavage fluid (to 149%) and to decrease significantly in the tracheal mucosa (-58%), however the content in bronchial mucosa was not significantly affected (-43%). Exposure to 15 ppm ammonia had no effect on the frequency of citric acid-induced coughing. In conclusion, ammonia inhibits citric acid-induced coughing in pigs at concentrations that can be detected in piggeries. This inhibitory effect may be related to substance-P depletion in C-fiber endings [less ▲]

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See detailEffet de l’ammoniac sur la fibre C impliquée dans le réflexe de la toux chez le porc
Moreaux, B.; Nemmar, R.; Gustin, Pascal ULg

in Journées de la Recherche Porcine en France (2000), 32

The effect of ammonia on the C-fibre which is involved in the citric acid induced coughing reflex was assessed. The piglets were exposed during a period of 24 hours or 4 days to a concentration of 15 or ... [more ▼]

The effect of ammonia on the C-fibre which is involved in the citric acid induced coughing reflex was assessed. The piglets were exposed during a period of 24 hours or 4 days to a concentration of 15 or 30 ppm ammonia in an inhalation chamber . During this challenge, the animais underwent cough induction tests at two days intervals. Another group was exposed to ammonia (30 ppm) for 48 hours, after this period, substance P was assayed in liquids collected from broncho-alvealor and tracheal washings (BAL and TAL) and in tracheal and airway mucosa . Ammonia (30 ppm) induced an inhibition 0f the coughing reflex in pigs. The minimum period of exposure necessary to provoke this effect was 48 hours. The same ammonia concentration aiso induced o significant increase in substance P concentrations in BAL and TAL and a significant decrease in concentrations of the tracheal mucosa. We conclude that ammonia at o concentration of 30 ppm inhibits the citric acid induced coughing reflex. The effect was partly mediated by the release of substance P from the C-fibre. [less ▲]

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See detailDevelopment of a Cough Induction Test in Pigs: Effects of Sr 48968 and Enalapril
Moreaux, B.; Beerens, Dominique ULg; Gustin, Pascal ULg

in Journal of Veterinary Pharmacology & Therapeutics (1999), 22(6), 387-389

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