Effects of endothelin B receptor antagonists, BQ788 and ET-1(11-21) fragment on the bronchoconstriction elicited by isocapnic hyperpnea in guinea pigs.
OBJECTIVE
To explore the role of endothelin (ET) in the pathogenesis of exercise-induced asthma (EIA), we investigated the effects of ETB receptor antagonists, ET-1(11-21) fragment and N-cis-2, 6-dimethylpiperidinocardonyl-L-gamma-methylleucyl-D-1-methoxycarbonyl tryptophanyl-D-norleucine (BQ788) on bronchoconstriction elicited by isocapnic hyperpnea in guinea pigs.


METHODS
Eighteen pathogen-free Hartley guinea pigs were randomly divided into three groups. A: normal saline (NS) inhalation control group (n = 6), B: BQ788 group (n = 6), and C: ET-1(11-21) fragment group (n = 6). Guinea pigs were anesthetized with pentobarbital sodium. After measuring the basal value of lung resistance (RL) and dynamic compliance of the respiratory system (Cdyn), NS (0.96 ml), BQ788 (9 nmol) and ET-1(11-21) fragment (9 nmol) were inhaled. A rodent respirator with a dry 5% CO(2)-95% O2 mixture at room temperature provided mechanical ventilation (VT8 ml/animal, 100 breaths/min) for 5 min. RL and Cdyn of the 3 groups were measured again after isocapnic hyperpnea challenge.


RESULTS
In the control group, isocapnic hyperpnea of dry gas elicited a marked increase in RL and decrease in Cdyn. RL and Cdyn of the guinea pigs from BQ788 group and ET-1(11-21) fragment group did not change significantly.


CONCLUSIONS
It was demonstrated that selective ETB receptor antagonists, ET-1(11-21) fragment and BQ788, inhibited the bronchoconstriction induced by isocapnic hyperpnea in guinea pigs. The data showed that ETs are potent constrictors of guinea pig airway smooth muscle via a direct effect on ET receptors. It was suggested that ET receptor antagonists, especially ETB receptor antagonist, might be beneficial in preventing EIA.
Liang
Y
Y
Department of Pulmonary Diseases, Zhongshan Hospital, Shanghai Medical University, Shanghai 200032, China.
Cai
Y
Y
D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D016084:Bronchoconstriction / Q000187:drug effects* / Q000502:physiology; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000494:pharmacology*; D006168:Guinea Pigs; D008170:Lung Compliance / Q000187:drug effects; D009842:Oligopeptides / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D044023:Receptor, Endothelin B
D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D009842:Oligopeptides; D010446:Peptide Fragments; D010880:Piperidines; D044023:Receptor, Endothelin B; C077420:Cys(11)-Cys(15)-endothelin-1 (11-21); C086539:BQ 788