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
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.