ENDOTHELIUM-DERIVED RELAXING FACTOR AS A MEDIATOR OF BRADYKININ-INDUCED PERINATAL PULMONARY VASODILATATION IN FETAL SHEEP

Studies in vivo in fetal sheep have shown that bradykinin is released following oxygenation of the lungs and is at least partly responsible for normal pulmonary vasodilatation in the transition from fetal to ex trauterine life. Part of this action involves secondary release of pro staglandin I-2 (PGI(2)). In various adult vessels, bradykinin also sti mulates the release of a powerful endothelium-derived relaxing factor (EDRF). Studies in vitro were designed (using a modification of the bi oassay cascade superfusion technique) to determine whether non-PGI(2)- related perinatal pulmonary vasodilatation is mediated by an EDRF. Sup erfused, precontracted, endothelium-denuded strips of fetal sheep thor acic aorta and the maternal sheep main pulmonary artery served as dete ctors of an EDRF released from isolated, perfused fetal sheep pulmonar y arteries. Bradykinin, in the presence of indomethacin to block PGI(2 ) synthesis, caused perfused fetal pulmonary arteries to release an ED RF, which generated a dose-dependent relaxation (24% for 1.0 mu M, 16. 8% for 0.1 mu M, and 10% for 0.01 mu M bradykinin). Thus, bradykinin c an produce perinatal pulmonary vasodilatation via a mechanism involvin g the endothelium-dependent Synthesis of an EDRF.