Elastase in hyperpnea-induced guinea pig airway constriction.
Aerosolized elastase has been shown to produce airway constriction in guinea pigs. In this study, we examined whether endogenous elastase plays a role in isocapnic hyperpnea-induced airway constriction using an elastase inhibitor, eglin-c. The study was divided into three experiments. In the first experiment, we used an elastase inhibitor, eglin-c, to suppress hyperpnea-induced bronchoconstriction. Twenty-two young male Hartley guinea pigs were divided into three groups: control (n=8), eglin-c(1) (a lower dose of eglin-c, n=7), and eglin-c(2) (a higher dose of eglin-c, n=7). In the second experiment, we tested whether eglin-c affects pulmonary function following 15 min of normal air ventilation in two groups of animals: control (n=8) and eglin-c (n=8). In the third experiment, animals were divided into two groups: control (n=7) and compound 48/80 (a mast cell degranulating agent, n=7). Airway function was examined in the anesthetized-paralyzed animal. In the first and third experiments, 15 min of isocapnic hyperpnea caused marked decreases in dynamic respiratory compliance, forced expiratory flow at 0.1 s and maximal expiratory flow at 50% total lung capacity, demonstrating hyperpnea-induced airway constriction. This bronchoconstriction was significantly attenuated by eglin-c and by pretreatment with compound 48/80. In the second experiment, eglin-c did not significantly affect bronchial function following normal air ventilation. These data suggest that elastase released from mast cells directly or indirectly induces hyperpnea-induced bronchoconstriction.
Lai
Y L
YL
Department of Physiology, College of Medicine, National Taiwan University, Taipei. tiger@ha.mc.ntu.edu.tw
Lin
Y J
YJ
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D016084:Bronchoconstriction / Q000187:drug effects / Q000502:physiology*; D006168:Guinea Pigs; D006985:Hyperventilation / Q000503:physiopathology*; D008168:Lung / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology; D008297:Male; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors / Q000502:physiology*; D010366:Peak Expiratory Flow Rate / Q000187:drug effects; D011506:Proteins; D012129:Respiratory Function Tests; D015843:Serpins / Q000494:pharmacology; D014797:Vital Capacity / Q000187:drug effects; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D011506:Proteins; D015843:Serpins; C028656:eglin proteinase inhibitors; D003189:p-Methoxy-N-methylphenethylamine; D010196:Pancreatic Elastase