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 extrauterine life. Part of this action involves secondary release of prostaglandin I-2 (PGI(2)). In various adult vessels, bradykinin also stimulates the release of a powerful endothelium-derived relaxing factor (EDRF). Studies in vitro were designed (using a modification of the bioassay cascade superfusion technique) to determine whether non-PGI(2)-related perinatal pulmonary vasodilatation is mediated by an EDRF. Superfused, precontracted, endothelium-denuded strips of fetal sheep thoracic aorta and the maternal sheep main pulmonary artery served as detectors of an EDRF released from isolated, perfused fetal sheep pulmonary arteries. Bradykinin, in the presence of indomethacin to block PGI(2) synthesis, caused perfused fetal pulmonary arteries to release an EDRF, 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 can produce perinatal pulmonary vasodilatation via a mechanism involving the endothelium-dependent Synthesis of an EDRF.