leukotriene-e4 and Hyperventilation

The role of mast cells in the airway response to exercise and the benefit of sodium cromoglycate (SCG) in athletes are unclear.. The purpose of this study was to clarify the role of mast cell mediators in the airway response to exercise in athletes and to investigate the effect of SCG.. Eleven athletes with exercise-induced bronchoconstriction (EIB+) and 11 without (EIB-) performed a eucapnic voluntary hyperpnea (EVH) test (a surrogate for exercise) 10 min after inhalation of a placebo or 40 mg of the mast cell stabilizing agent sodium cromoglycate. The urinary concentrations of 9a,11β-PGF2 (a metabolite of PGD2 and a marker of mast cell activation) and leukotriene E4 (LTE4) were measured by enzyme immunoassay 60 min before and for 90 min after the challenge.. In the EIB+ group, the maximum fall in forced expiratory volume in 1 s (FEV1) of 20.3% ± 3% on placebo was reduced to 11.5% ± 1.9% after SCG (P = 0.003). There was an increase in the urinary excretion of 9α,11β-PGF2 on the placebo day after EVH in both groups (P < 0.05) that was abolished by SCG. In the EIB+ group, there was also an increase of urinary LTE4 on the placebo day that was abolished by SCG, whereas the urinary excretion of LTE4 was inconsistent in the EIB- group.. The results support mast cell activation with release of bronchoconstrictive mediators after hyperpnea in athletes with and without EIB and inhibition by SCG. The degree of airway responsiveness to the specific mediator released is likely to determine whether or not bronchoconstriction will occur after EVH.

Topics: Adrenergic Agonists; Adult; Androstadienes; Asthma, Exercise-Induced; Athletes; Bronchodilator Agents; Cromolyn Sodium; Dinoprost; Exercise Test; Female; Fluticasone; Forced Expiratory Volume; Humans; Hyperventilation; Inflammation Mediators; Leukotriene E4; Male; Mast Cells; Young Adult

Inhalation of heparin attenuates hyperventilation-induced bronchoconstriction in humans and dogs. The purpose of this study was to determine whether heparin inhibits the late-phase response to hyperventilation, which is characterized by increased peripheral airway resistance (RP), eicosanoid mediator production, neutrophilic/ eosinophilic inflammation, and airway hyperreactivity (AHR) at 5 h after dry air challenge (DAC). Fiberoptic bronchoscopy was used to record RP and airway reactivity (DeltaRP) to aerosol and intravenous histamine before and 5 h after DAC. Bronchoalveolar lavage fluid (BALF) cells and eicosanoid mediators were also measured approximately 5 h after DAC. DAC of vehicle-treated bronchi resulted in late-phase airway obstruction (approximately 120% increase over baseline RP), inflammation, increased BALF concentrations of leukotriene (LT) C(4), LTD(4), and LTE(4) and prostaglandin (PG)D(2), and AHR. Pretreatment with aerosolized heparin attenuated late-phase airway obstruction by approximately 50%, inhibited eosinophil infiltration, reduced BALF concentrations of LTC(4), LTD(4), and LTE(4) and PGD(2), and abolished AHR. We conclude that heparin inhibits hyperventilation-induced late-phase changes in peripheral airway function, and does so in part via the inhibition of eosinophil migration and eicosanoid mediator production and release.

Topics: Administration, Inhalation; Airway Resistance; Animals; Bronchial Hyperreactivity; Bronchial Provocation Tests; Bronchoalveolar Lavage Fluid; Bronchoscopy; Disease Models, Animal; Dogs; Drug Evaluation, Preclinical; Eicosanoids; Eosinophils; Heparin; Humans; Hyperventilation; Inflammation; Leukotriene C4; Leukotriene D4; Leukotriene E4; Male; Neutrophils; Prostaglandin D2; Time Factors

Previous studies have indicated that increased dietary salt consumption worsens postexercise pulmonary function in humans with exercise-induced asthma (EIA). It has been suggested that EIA and hyperpnea-induced airway obstruction (HIAO) in guinea pigs (an animal model of EIA) are mediated by similar mechanisms. Therefore, the purpose of this study was to determine whether altering dietary salt consumption also exacerbated HIAO in guinea pigs. Furthermore, the potential pathway of action of dietary salt was investigated by blocking leukotriene (LT) production during HIAO in guinea pigs. Thirty-two male Hartley strain guinea pigs were split into two groups. One group (n = 16) of animals ingested a normal-salt diet (NSD) for 2 wk; the other group (n = 16) ingested a high-salt diet (HSD) for 2 wk. Thereafter, animals were anesthetized, cannulated, tracheotomized, and mechanically ventilated during a baseline period and during two dry gas hyperpnea challenges. After the first challenge, the animals were administered either saline or nordihydroguaiaretic acid, a LT inhibitor. Bladder urine was analyzed for electrolyte concentrations and urinary LTE(4). The HSD elicited higher airway inspiratory pressures (Ptr) than the NSD (P < 0.001) postchallenge. However, after infusion of the LT inhibitor and a second hyperpnea challenge, HIAO was blocked in both diet groups (P < 0.001). Nonetheless, the HSD group continued to demonstrate slightly higher Ptr than the NSD group (P < 0.05). Urinary LTE(4) excretion significantly increased in the HSD group compared with the NSD group within treatment groups. This study has demonstrated that dietary salt loading exacerbated the development of HIAO in guinea pigs and that LT release was involved in HIAO and may be moderated by changes in dietary salt loading.

Topics: Airway Obstruction; Animals; Body Weight; Bronchoconstriction; Eating; Electrolytes; Guinea Pigs; Hyperventilation; Leukotriene E4; Lipoxygenase Inhibitors; Male; Masoprocol; Physical Exertion; Sodium Chloride; Sodium Chloride, Dietary