Kinins: possible mediators of neonatal circulatory changes in man

Abstract

Bradykinin is a potent constrictor of the human umbilical artery and vein and the ductus arteriosus of the lamb in vitro at oxygen tensions above 40 mm Hg (comparable to those in the newborn infant). Bradykinin is also capable of producing remarkable dilatation of the pulmonary vasculature of the lamb. Theoretically, kinins are capable of effecting some of the rapid circulatory changes required of the neonate. The present study was undertaken to investigate the role of kinins as mediators of such changes. The concentration of bradykinin in the cord blood of 56 newborn infants at the time of birth was significantly higher than the blood level in adult subjects (12.8 +/- 4.3 ng/ml compared with 2.0 ng/ml or less). Cord arterial blood contained inactive kinin precursor (kininogen) and inactive kinin-releasing enzyme (kallikrein). Plasma kallikrein was activated, with subsequent kinin formation and kininogen depletion, by exposure to neonatal granulocytes or by a decrease in the temperature of cord blood from 37 to 27 degrees C. A comparable decrease in the temperature of umbilical arterial blood occurs at the time of birth. Activation of kallikrein by neonatal granulocytes was dependent on cell concentration and required oxygen tensions comparable to those in the neonate but above the range in the fetus. Granulocytes of the neonate, unlike those of adult subjects, lacked kininase activity.Thus, bradykinin can constrict and dilate vessels as required for the transition of fetal to neonatal circulation. Bradykinin can be produced in plasma of the newborn by decreases in temperature, such as occur in the umbilical blood at birth, and by exposure to granulocytes which are present in the circulation in increased numbers shortly after birth. We propose that bradykinin is produced at birth and may be a mediator of neonatal circulatory changes.