The ETA antagonist CI-1020 inhibits hypoxic pulmonary vasoconstriction in small isolated rat pulmonary arteries

Hypoxic pulmonary vasoconstriction (HPV) of rat pulmonary arteries in vitro occurs in four phases, Initial vasodilation (phase 1), is followed by transient contraction (phase 2), further vasodilation (phase 3) and finally a second sustained contraction (phase 4), We have investigated the role of ET-1 in HPV using the ETA receptor antagonist CI-1020, Small rat pulmonary arteries (SPA, n=32, diameter=454+/-22 pill) were mounted in a wire myograph, Two contractions to 80 mu M KCl ensured response reproducibility and relaxation to 10 mu M acetyl choline following constriction with 100 mu M prostaglandin F-2 alpha (PGF(2 alpha)) to indicate endothelial integrity. A control hypoxic response was produced following priming with 5 mu M PGF(2 alpha). Vessels (n = 8) were then exposed to either vehicle or CI-1020 (1, 10 or 100 mu M) for 30 min in the dark before re-exposure to PGF(2 alpha) and hypoxia, Responses were standardized as a percentage of contraction to 80 mM KCI, Vehicle caused an increase in phase 2 of HPV of +2.51+/-4.20% (expressed as difference between pre- and post-drug values). CI-1020 (1, 10 and 100 mu M) caused a significant reduction in phase 2 of HPV of -9.76+/-1.40%, -9.23+/-2.30% and -7.96+/-1.70%, respectively (P<0.05). These results suggest that phase 2 of HPV in rat SPA is attributed, in part, to the action of ET-1 at the ETA receptor. (C) 1998 Academic Press.