The endothelin-A-receptor antagonist PD 180988 (CI-1034) selectively reverses the pulmonary vasoconstrictor response to hypoxia in the lamb.
Endothelin-1 (ET-1) is assigned a mediator role in the constrictor response of the pulmonary vasculature to hypoxia. Accordingly, a recently developed endothelin-A (ETA) antagonist, PD180988, was tested in the chronically instrumented newborn lamb to verify this possibility and, at the same time, to study a potential new treatment for pulmonary hypertension (PH). PD180988, given by infusion after a priming bolus, had an insignificant effect on the pulmonary circulation under normoxia, while it reversed the sustained pulmonary constriction caused by hypoxia. No appreciable change was noted under either experimental condition in the systemic circulation and cardiac contractility. We conclude that PD180988 is a selective inhibitor of hypoxic pulmonary vasoconstriction and lends itself to therapeutic use in infants.
Coe
Y
Y
Department of Pediatrics, University of Alberta, Edmonton, Canada.
Haleen
S J
SJ
Welch
K M
KM
Coceani
F
F
D000818:Animals; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000097:blood; D000860:Hypoxia / Q000503:physiopathology*; D011652:Pulmonary Circulation / Q000187:drug effects*; D044022:Receptor, Endothelin A; D012756:Sheep; D013843:Thiazines / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*
D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; C419982:PD 180988; D044022:Receptor, Endothelin A; D013843:Thiazines