ETA receptor blockade potentiates the bronchoconstrictor response to ET-1 in the guinea pig airway.
The effect of ETA receptor blockade on the bronchopulmonary response to endothelin-1 was determined in the airway of the anesthetized, spontaneously breathing guinea pig. Endothelin-1 administered as an aerosol increased lung resistance and decreased dynamic lung compliance. Delivery of the ETA receptor antagonist, FR139317, 5 min prior to giving endothelin-1 greatly potentiated these changes. A lower dose of endothelin-1 that had no effect on resistance or compliance produced large and significant changes when pretreated with FR139317. In contrast, aerosolized FR139317 had no effect on the bronchopulmonary response to intravenously administered endothelin-1. These data suggest a non-contractile function of ETA receptors accessible from the airways that serve to buffer the constrictor effects of non-ETA receptors.
Polakowski
J S
JS
Abbott Laboratories, Abbott Park, Illinois 60064, USA. Jim.Polakowski@Abbott.com
Opgenorth
T J
TJ
Pollock
D M
DM
D000336:Aerosols; D000704:Analysis of Variance; D000818:Animals; D001381:Azepines / Q000008:administration & dosage / Q000494:pharmacology; D001980:Bronchi / Q000187:drug effects / Q000502:physiology; D016085:Bronchoconstrictor Agents / Q000494:pharmacology*; D004334:Drug Administration Schedule; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000008:administration & dosage / Q000494:pharmacology*; D006168:Guinea Pigs; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000502:physiology*; D008170:Lung Compliance / Q000187:drug effects; D008297:Male; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin / Q000502:physiology; D013997:Time Factors
D000336:Aerosols; D001381:Azepines; D016085:Bronchoconstrictor Agents; D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D007211:Indoles; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin; C079574:FR 139317