Endothelin-1 in Citric Acid Aerosol Inhalation-Induced Airway Constriction of Guinea Pigs

S. C. Lee；Y. L. Lai

airway reactivity ； acid-induced airway constriction ； endothelins

The Chinese Journal of Physiology

45卷1期（2002 / 03 / 01）

25 - 31

英文

Endotheline-1 (ET-1) has been shown to enhance tachykinin-induced airway constriction. This study was designed to test whether ET-1 is involved in citric acid-induced bronchoconstriction. Forty-eight anesthetized-paralyzed guinea pigs were divided into six groups of 8 animals each: saline control; citric acid; ET-1; ET-1 + citric acid; BQ123+ET-1+citric acid; and BQ788 + ET-1 +citric acid. BQ123 and BQ788 are specific ET(subscript A) and ET(subscript B) receptor antagonists, respectively. Each animal in the saline control group received 50 breaths of 4 ml saline aerosol and in all citric acid-treated groups was given 50 breaths of 4 ml aerosol generated from 0.6 M citric acid. In all ET-1-treated groups, each animal was exposed to aerosol generated from 10^(-8) M ET-1. The animal in the ET-1 + citric acid group was exposed to ET-1 5 min prior to the citric acid. For the last two groups, each animal was first exposed to aerosol generated from either 10^(-5) M BQ123 or 10^(-5) M BQ788. Five mm later, the animal was exposed to ET-1; and then 5 min later was followed by citric acid. Dynamic respiratory compliance (Crs), forced expiratory volume in 0.1 sec (FEV0.1), and maximal expiratory flow at 30% total lung capacity (Vmax30) were obtained before and 3-15 mm after citric acid. Either citric acid or ET-1 inhalation caused significant decreases in Crs, FEV0.1, and Vmax30, indicating airway constriction. Citric acid-induced airway constriction, for most cases, was not significantly augmented by ET-1. However, either BQ123 or BQ 788 significantly attenuated the airway constriction induced by the combination of ET-1 and citric acid. Also, in an additional study, either BQ123 or BQ788 significantly attenuated citric acid-induced airway constriction. These data suggest that endogenous ET-1 plays an important role in citric acid aerosol-induced airway constriction in guinea pigs.

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