HYPERPNEA-INDUCED BRONCHOCONSTRICTION IS DEPENDENT ON TACHYKININ-INDUCED CYSTEINYL LEUKOTRIENE SYNTHESIS

Citation
Xx. Yang et al., HYPERPNEA-INDUCED BRONCHOCONSTRICTION IS DEPENDENT ON TACHYKININ-INDUCED CYSTEINYL LEUKOTRIENE SYNTHESIS, Journal of applied physiology, 82(2), 1997, pp. 538-544
Citations number
41
Categorie Soggetti
Physiology,"Sport Sciences
ISSN journal
87507587
Volume
82
Issue
2
Year of publication
1997
Pages
538 - 544
Database
ISI
SICI code
8750-7587(1997)82:2<538:HBIDOT>2.0.ZU;2-I
Abstract
Hyperpnea-induced bronchoconstriction is dependent on tachykinin-induc ed cysteinyl leukotriene synthesis. J. Appl. Physiol. 82(2): 538-544, 1997.-The purpose of the study was to test the hypothesis that tachyki nins mediate hyperpnea; induced bronchoconstriction indirectly by trig gering cysteinyl leukotriene (LT) synthesis in the airways. Guinea pig s (350-600 g) were anesthetized with xylazine and pentobarbital sodium and received hyperpnea challenge (tidal volume 3.5-4.0 ml, frequency 150 breaths/min) with either humidified isocapnic gas (n = 6) or dry g as (n = 7). Dry gas challenge was performed on animals that received M K-571 (LTD(4) antagonist; 2 mg/kg iv; n = 5), capsaicin (n = 4), neuro kinin (NK) antagonists [NK1 (CP-99994) + NK2 (SR-48968) (1 mg/kg iv); n = 6], or the H-1 antihistamine pyrilamine (2 mg/kg iv; n = 5). We me asured the tracheal pressure and collected bile for 1 h before and 2 h after hyperpnea challenge. We examined the biliary excretion of cyste inyl LTs; the recovery of radioactivity in bile after instillation of 1 mu Ci [H-3]LTC(4) intratracheally averaged 24% within 4 h (n = 21. T he major cysteinyl LT identified was LTD(4) (32% recovery of radioacti vity). Cysteinyl LTs were purified from bile of animals undergoing hyp erpnea challenge by using reverse-phase high-pressure liquid chromatog raphy and quantified by radioimmunoassay. There was a significant incr ease in the peak value of tracheal pressure after challenge, indicatin g bronchoconstriction in dry gas-challenged animals but not after humi dified gas challenge. MK-571, capsaicin, and NK antagonists prevented the bronchoconstriction; pyrilamine did not. Cysteinyl LT levels in th e bile after challenge were significantly increased from baseline in d ry gas-challenged animals (P < 0.05) and were higher than in the anima ls challenged with humidified gas or dry gas-challenged animals treate d with capsaicin or NK antagonists (P < 0.01). The results indicate th at: isocapnic dry gas hyperpnea-induced bronchoconstriction is LT medi ated and the role of tachykinins in tile response is indirect through release of LTs. Endogenous histamine does not contribute to the respon se.