Endothelin A receptor is necessary for O2 constriction but not closure of ductus arteriosus

In vitro and in vivo techniques were developed with genetically modified mice to determine whether endothelin-1 (ET-1) functions as an O2 mediator in closure of the ductus arteriosus (DA) at birth. Wild-type CD-1 and 129/SvEv mice with ET(A) receptor -/-, +/-, and +/+ genotypes were used. Isolated DA from term ET(A) +/+ fetuses contracted to O2 (5-95%) and a thromboxane A2 analog (ONO-11113, 0.1 μM). Instead, ET-1 elicited a dual response with …