Endothelin-1-endothelin receptor type A mediates closure of rat ductus arteriosus at birth

1. The ductus arteriosus (DA) undergoes rapid closure after birth as pulmon ary circulation is established. The involvement of endothelin-1 (ET1) in th is closure mechanism is controversial. 2. The effect of ATZ1993 (ATZ), a non-peptide antagonist for the ETA 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 Cae sarean section and were given ATZ intraperitoneally. The minimum external D A diameter and the extent of DA constriction in vivo were evaluated at 2.5 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 w as observed. 3. In vitro, ATZ also caused a marked inhibition of O-2-induced and ET1-ind uced DA contractions as did BQ123, an ETA-specific antagonist. In contrast, sarafotoxin S6c, an ETB-specific agonist, did not cause DA contraction and BQ788, an ETB-specific antagonist, did not affect O-2-induced DA contracti on. 4. In conclusion, ET1 and its cognate receptor ETA may play a physiological role in the postnatal closure of the rat DA in vivo.