Mediators in hyperpnea-induced bronchoconstriction of guinea pigs.
Both tachykinins and leukotrienes (LTs) have been demonstrated to be the mediators for hyperpnea-induced bronchoconstriction (HIB) of guinea pigs. We tested the hypothesis that leukotrienes modulate HIB indirectly by triggering tachykinin release. Ninety nine young guinea pigs were divided into four groups: control; LTC4; FPL 55712 (a LT receptor antagonist); and MK-886 (an inhibitor of LT synthesis). Each animal was anesthetized, cannulated, paralyzed, and artificially ventilated. The protocol included the baseline, hyperpnea, and recovery periods. Thus, animals in each group were further divided into three subgroups: baseline; recovery-3 min; and recovery-8 min. We measured dynamic respiratory compliance (Crs), forced expiratory volume in 0.1 s (FEV0.1) and maximal expiratory flow at 30% total lung capacity (Vmax30), as well as determined substance P (SP) and LT levels in plasma and bronchoalveolar lavage (BAL) during either the baseline or the recovery (3 or 8 min) period. Hyperpnea caused decreases in Crs, FEV0.1 and Vmax30, indicating HIB, in the control group at 3 min and 8 min of the recovery period. Both FPL 55712 and MK-886 significantly attenuated HIB. In the control group, hyperpnea caused significant increases in SP and LT levels in both plasma and BAL. These increases in SP levels were significantly suppressed, however, by FPL 55712 and MK-886. Compared to the control group, infusion of LTC4 did not significantly alter either HIB, SP or LT levels in most cases. An additional group of 24 animals treated with neurokinin-2 receptor antagonist, SR 48968, demonstrated that SR 48968 significantly suppressed hyperpnea-induced increases in plasma, but not in BAL, LT levels. Since FPL 55712 and MK-886 first suppress LT activities, these results suggest that suppressed LT activities attenuate HIB indirectly via reducing tachykinin release.
Lai
Y L
YL
Department of Physiology, National Taiwan University College of Medicine, Taipei.
Lee
S P
SP
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016084:Bronchoconstriction / Q000502:physiology*; D002867:Chromones / Q000494:pharmacology; D005541:Forced Expiratory Volume / Q000187:drug effects; D006168:Guinea Pigs; D007211:Indoles / Q000494:pharmacology; D020024:Leukotriene Antagonists / Q000494:pharmacology; D015289:Leukotrienes / Q000097:blood / Q000502:physiology*; D008170:Lung Compliance / Q000187:drug effects; D008448:Maximal Expiratory Flow Rate / Q000187:drug effects; D018077:Receptors, Leukotriene / Q000187:drug effects; D012121:Respiration, Artificial; D015656:Respiratory Mechanics / Q000502:physiology*; D013373:Substance P / Q000097:blood; D015320:Tachykinins / Q000378:metabolism / Q000502:physiology*; D013997:Time Factors; D014109:Total Lung Capacity / Q000187:drug effects; D002722:Chlorobenzenes
D002867:Chromones; D007211:Indoles; D020024:Leukotriene Antagonists; D015289:Leukotrienes; D018077:Receptors, Leukotriene; D013373:Substance P; D015320:Tachykinins; C060893:MK-886; D002722:Chlorobenzenes; C006312:FPL 55712