AJP - Lung Cellular and Molecular Physiology, Vol 268, Issue 5 846-L850, Copyright © 1995 by American Physiological Society
In vivo effects of endothelin A- and B-receptor antagonists in guinea pigs
T. Nagase, Y. Fukuchi, H. Matsui, T. Aoki, T. Matsuse and H. Orimo
Department of Geriatrics, Faculty of Medicine, University of Tokyo, Japan.
Endothelin (ET)-1, a novel 21-amino acid constrictor peptide, has been
recently reported to have a potential pathophysiological role in asthma. We
hypothesized that ET-1 might affect guinea pig lung via different ET
receptor subtypes, i.e., ETA and ETB, in vivo. To test this hypothesis, we
investigated the effects of ET-1 on airways in anesthetized, open-chest,
mechanically ventilated [frequency (f) = 1 Hz; tidal volume (VT) = 9 ml/kg;
positive end-expiratory pressure (PEEP) = 4 cmH2O] guinea pigs in the
absence or the presence of ETA and ETB selective antagonists, i.e., BQ-123
and BQ-788, respectively. We affixed alveolar capsules to the lungs to
measure alveolar pressure and calculated the elastance of lung (EL) and the
resistance of lung (RL), tissue (Rti), and airway (R(aw)) under control
conditions and after intravenous administration of ET-1 (10(-8) mol/kg).
ET-1 induced a concentration-dependent increase in RL, Rti, R(aw), and
EL.BQ-123 (2 mg/kg) partially blocks delta RL and delta R(aw) during ET-1
induced constriction, while delta Rti and delta EL were not significantly
affected. BQ-788 (2 mg/kg) significantly inhibited delta RL, delta Rti,
delta R(aw), and delta EL during ET-1-induced constriction. The combination
of BQ-123 and BQ-788 completely ablated the response to ET-1. These data
suggest that both ET receptor subtypes, i.e., ETA and ETB, may have
physiological roles in guinea pig airways in response to ET-1, a potential
mediator of asthma.
