AIRWAY AND LUNG-TISSUE BEHAVIOR DURING ENDOTHELIN-1 INDUCED CONSTRICTION IN RATS - EFFECTS OF RECEPTOR ANTAGONISTS

Endothelin (ET) 1, a 21 amino acid constrictor peptide, is one of the most potent agonists of airway smooth muscle and acts on two different receptors, i.e., ETA and ETB receptors. Recently, it has been shown t hat there are species and organ differences in physiological roles of each ET receptor. In rats, however, the physiological roles of ET rece ptors remain to be clarified. We questioned whether ET-1 might affect ah-way and lung tissue via different ET receptor subtypes in rats. To answer this question, we investigated the effects of ET-1 on lung beha viour in anesthetized, open-chested, mechanically ventilated (f = 1 Hz , V-T = 9 mL/kg, PEEP = 3 cmH(2)O (1 cmH(2)O = 98.1 Pa)) rats in the a bsence or the presence of ETA and ETB selective antagonists, i.e., BQ- 123 and BQ-788, respectively. Using alveolar capsules, we calculated l ung elastance (E-L), resistance of lung (R-L), tissue (Rti), and airwa y (Raw), and hysteresivity (eta = 2 pi fRti/E-L) under control conditi ons and after intravenous administration of ET-1 (10(-8) mol/kg). ET-1 induced significant increases in R-L, Rti, Raw, E-L, and eta. BQ-123 did not affect ET-1 induced constriction, while BQ-788 significantly r educed Delta R-L, Delta Rti, Delta Raw, and Delta E-L during ET-1 indu ced constriction. The effects of the combination of BQ-123 and BQ-788 were not different compared with BQ-788. eta was not affected by BQ-12 3 and BQ-788. These data suggest that ETB, but not ETA, receptors may have significant physiological roles in rat lungs in response to ET-1.