Bradykinin Production Associated with Oxygenation of the Fetal Lamb

Previous studies showed that synthetic bradykinin produced in-vitro constriction of the ductus arteriosus of the fetal lamb and guinea pig, constriction of isolated human and lamb umbilical vessels, and pulmonary vasodilatation in the fetal lamb. The present study showed that bradykinin precursor, kininogen, is present in arterial blood of the fetal lamb by 61 days of gestation and that its concentration increases toward term. We studied the bradykinin-generating system in 6 exteriorized fetal lambs. Kininogen concentrations in left atrial blood decreased within 1 to 2 minutes after beginning ventilation with O 2 , and free bradykinin was detected in left atrial blood. Pulmonary arterial blood kininogen concentration was not significantly altered. Kininogen concentration in left atrial blood did not fall in 4 other lambs ventilated with N 2 but did fall after subsequent ventilation with O 2 . To study the effects of increased oxygenation in utero without lung expansion, 6 pregnant ewes were exposed to hyperbaric O 2 at 3.63 atmospheres absolute. Associated with a mean increase in brachial arterial blood Po 2 to 44 mm Hg, a value equivalent to that in the ventilated exteriorized fetus, kininogen concentration fell, and free bradykinin was detected in the brachial arterial blood of 3 of the 6 fetuses. In 4 other exteriorized lambs we measured kininogen concentration in brachial arterial and right ventricular blood at frequent intervals up to 30 minutes after ventilation with O 2 . The concentration in brachial arterial blood fell before that in right ventricular blood. The hypothesis is presented diat bradykinin is produced from kininogen in the lungs of the fetal lamb when oxygenated, and that the maximal rate of production occurs during the first few minutes after expansion of the lungs or exposure of the ewe and fetus to hyperbaric O 2 .