verlukast and Asthma--Exercise-Induced

Topics: Asthma; Asthma, Exercise-Induced; Humans; Lung; Propionates; Quinolines; Receptors, Immunologic; Receptors, Leukotriene; SRS-A

Exercise is a common stimulus of bronchoconstriction in subjects with asthma, who also have bronchoconstriction after inhaling the sulfidopeptide leukotriene D4 (LTD4). The purpose of this study was to investigate the importance of LTD4 as a mediator of exercise-induced bronchoconstriction.. In a double-blind, randomized, crossover study, 12 subjects with stable asthma were treated intravenously with MK-571 (160 mg), a selective and potent LTD4-receptor antagonist, or placebo, 20 minutes before each of two challenges involving exercise at a level previously demonstrated to cause a fall of at least 20 percent in the forced expiratory volume in one second (FEV1). The two exercise challenges were separated by one week. The results of the challenges were expressed as both the maximal fall in FEV1 after exercise and the time to recovery from bronchoconstriction.. Treatment with MK-571 attenuated exercise-induced bronchoconstriction in all the subjects. The mean (+/- SEM) maximal percent decrease in FEV1 after exercise was 25.2 +/- 3.5 percent in the subjects taking placebo and 9.2 +/- 2.5 percent in the subjects taking MK-571 (P less than 0.001). The mean percent inhibition for the entire group was 69.5 percent. The mean time to recovery after exercise was 33.4 +/- 4.0 minutes in the placebo group and 8.4 +/- 2.5 minutes in the MK-571 group (P less than 0.001).. This study demonstrates that pretreatment with a potent and selective LTD4 antagonist markedly attenuates exercise-induced bronchoconstriction, and it suggests that LTD4 is a major mediator of this type of bronchoconstriction.

Topics: Asthma, Exercise-Induced; Bronchoconstriction; Double-Blind Method; Forced Expiratory Volume; Humans; Propionates; Quinolines; Receptors, Immunologic; Receptors, Leukotriene; SRS-A

It has been reported that hyperpnea-induced bronchoconstriction in guinea pigs is a potential model for exercise-induced asthma in humans. We hypothesized that calcitonin gene-related peptide (CGRP) could modulate leukotriene D4 (LTD4)-induced responses and be involved in the pathophysiology in this asthma model. We measured tracheal (Ptr) and alveolar pressure (PA) using alveolar capsules in open-chested, mechanically ventilated (f = 1 Hz, VT = 9 ml/kg, PEEP = 4 cm H2O) guinea pigs. Animals were intravenously pretreated with saline (SAL), CGRP(8-37) (CGRP receptor antagonist), CGRP, MK-571 (LTD4 receptor antagonist), MK-886 (5-lipoxygenase inhibitor), or CGRP(8-37) + MK-571, and then underwent dry gas hyperpnea challenge (HC, 95% 02-5% CO2, 150 breaths/min, 7 min). We calculated resistance of lung (RL), tissue (Rti), and airway (Raw). HC increased RL, Rti, and Raw in SAL controls (322 +/- 27, 430 +/- 59, 299 +/- 23% baseline, respectively). MK-571, MK-886, and CGRP significantly reduced the responses to HC, while CGRP(8-37) enhanced HC-induced responses. Pretreatment with CGRP(8-37) and MK-571 in combination attenuated HC-induced constriction. In addition, pretreatment with CGRP reduced responses induced by intravenous administration of LTD4. These observations suggest that CGRP might be involved in the pathophysiology of hyperpnea-induced constriction in guinea pigs via modulation of LTD4-elicited responses.

Topics: Animals; Asthma, Exercise-Induced; Bronchoconstriction; Bronchodilator Agents; Calcitonin Gene-Related Peptide; Drug Interactions; Guinea Pigs; Hyperventilation; Indoles; Leukotriene D4; Lipoxygenase Inhibitors; Male; Miotics; Models, Biological; Peptide Fragments; Positive-Pressure Respiration; Propionates; Quinolines; Respiration, Artificial

Topics: Asthma, Exercise-Induced; Bronchoconstriction; Humans; Propionates; Quinolines; Receptors, Immunologic; Receptors, Leukotriene; SRS-A