EFFECTS OF CAPTOPRIL ON THE HUMAN FETAL-PLACENTAL CIRCULATION - AN INTERACTION WITH BRADYKININ AND ANGIOTENSIN-I

1 The mechanism underlying the foetal toxicity induced by captopril is not well understood. Since bradykinin and angiotensin II appear to be important in the regulation of the placental circulation, experiments were performed to assess the effects of captopril on the vascular act ions of these peptides on the human foetal placental circulation. 2 Fu ll-term human placentas, obtained from normal pregnancy, were perfused with a modified Tyrode solution bubbled with O-2 using a pulsatile pu mp. The placental perfusion pressure was measured with a Statham press ure transducer and recorded continuously on a Hewlett-Packard polygrap h. 3 Bradykinin (0.1, 0.3 and 1.0 nmol) injected into the placental ar terial circulation produced an increase in placental perfusion pressur e in all experiments. This effect of bradykinin was significantly inhi bited by indomethacin (3 x 10(-7) M). 4 Captopril (10(-7) M) significa ntly potentiated the presser effect of bradykinin on the human placent al circulation (n = 6). This effect of captopril was reversed by indom ethacin (3 x 10(-7) M). 5 Angiotensin I (n = 6) and angiotensin II (n = 6), injected into the placental arterial circulation, both produced dose-dependent increases in placental perfusion pressure. The dose-res ponse curves to angiotensin I (n = 6) were significantly displaced to the right by captopril in a concentration-dependent manner. 6 We sugge st that the toxic effects of captopril on the foetus, rather than refl ecting an inhibition of angiotensin II formation, may instead be relat ed to a potentiation of the vasoconstrictor effect of bradykinin on th e foetal placental circulation, thereby reducing blood flow and causin g foetal damage. The reasons for this are discussed. 7 In addition, ou r results also suggest that the vasoconstrictor effects of bradykinin may be due to a release of vasoconstrictor prostanoid substances.