Role of endothelin in the physiological closure of Ductus Artenosus

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1)Ductus arteriosus(DA) undergoes rapid closure after birth as pulmonary circulation is established The mechanism of the closure is controversial regarding an involvement of endothelin(ET).2)The effect of ATZ1993(ATZ), a non-peptide antagonist for the ET_A and ET_B receptors, on postnatal closure and O_2-induced contraction of the rat DA was investigated both in vivo and in vitro. Rat pups were delivered by Caesarean section and were given ATZ intraperitoneally. The minimum external DA diameter and the extent of DA constriction in vivo were evaluated at 25 h after birth. ATZ caused a dose-dependent inhibition of DA closure in vivo. When rat pups were given ATZ at 2.5 h after birth, re-opening of the DA was observed.3)In vitro, ATZ also caused a marked inhibition of O_2-induced and ET1-induced DA contractions as did BQ123, a ET_A-specific antagonist. In contrast, sarafotoxin S6c, an ET_B-specific agonist, did not cause DA contraction and BQ 788, an ET_B-specific antagonist, did not affect O_2-induced DA contraction.4)ET and its cognate receptor ET_A can play a physiological role in the postnatal closure of the rat DA in vivo.