Although many
protease exist in human placenta, their physiologic roles are still unknown. Our study showed that placenta
proteases metabolize vasoactive
peptides possibly derived from the fetus. Because
vasopressin and
angiotensin are known to play an important role in normal and aberrant (
preeclampsia) fetal-placental circulation, the clearance of these
peptides in the placenta is important in controlling fetal blood pressure.
Vasopressin and
angiotensin act as a fetal-placental
vasoconstrictor; therefore, placental
proteases in human placenta are likely to work as a clearance factor for these
peptides. Although human and animal pregnancy is normally associated with a refractory response to the pressor effect of exogenously infused
angiotensin II, patients with
preeclampsia, as well as nonpregnant women, are sensitive to the pressor effect of
angiotensin II. Our study suggested that the decreased pressor responsiveness to
angiotensin II in pregnancy is caused by increased inactivation of
angiotensin II by
angiotensinase in pregnant serum and the placenta. Although
vasopressinase and
angiotensinase activities increase with advancing gestation in normal pregnant sera, the activities of both
enzymes in severe
preeclampsia sera were clearly lower than those in normal pregnancy. Therefore, it is reasonable to speculate that the increased sensitivity to
angiotensin II of
preeclampsia is attributable to the decreased degradation of
angiotensin II by placental
angiotensinase. The negative correlations between the systolic to diastolic ratio obtained from pulsed Doppler measurement techniques and the activities of both
enzymes in
preeclampsia sera suggested that the systolic to diastolic ration, which reflected constriction of placental vessels, is influenced by the concentration of vasoactive
peptides in the fetal-placental circulation due to changes in the activities of placental
proteases. Placental
proteases play important roles in controlling fetal and maternal blood pressure through regulation of the concentration of vasoactive
peptides in the interface (placenta) between fetus and mother.