Endothelin-1 in citric acid aerosol inhalation-induced airway constriction of guinea pigs.

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 ETA and ETB 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 min 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 (FEV(0.1)), and maximal expiratory flow at 30% total lung capacity (Vmax 30) were obtained before and 3-15 min after citric acid. Either citric acid or ET-1 inhalation caused significant decreases in Crs, FEV(0.1), and Vmax 30, 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.