Canine Pulmonary Arterial and Venous Responses Mediated by Endothelin ETA and ETB Receptors

Abstract

Endothelin (ET)-1 and ET-3 elicited relaxations at 1 nM and contractions at 10 nM or higher, whereas IRL1620 induced only relaxation in dog pulmonary arteries. The relaxations by ET-1, ET-3 and IRL1620 were not affected by indomethacin, but were abolished by endothelium denudation or NG-nitro-L-arginine. The relaxations caused by ET-3 and IRL1620 were markedly suppressed by IRL1038. BQ123 potentiated ET-1-, ET-3- and IRL1620-induced relaxations and markedly suppressed ET-1- and ET-3-induced contractions. ET-1, ET-3 and IRL1620 produced only contraction in pulmonary venous strips; the order of potency was ET-1 > ET-3 > IRL1620. The contraction induced by ET-1 was markedly suppressed by BQ123. This ETA antagonist also suppressed the ET-3-induced contraction. Under ETA receptor blockade, EŤ-3 (30 nM) produced endothelium-independent relaxation, which was abolished by indomethacin. IRL1038 suppressed the IRL1620-induced contraction. It is concluded that pulmonary arterial and venous responses to ET can be att...