Effects of captopril on the human foetal 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 actions of these peptides on the human foetal placental circulation. 2. Full-term human placentas, obtained from normal pregnancy, were perfused with a modified Tyrode solution bubbled with O2 using a pulsatile pump. The placental perfusion pressure was measured with a Statham pressure transducer and recorded continuously on a Hewlett-Packard polygraph. 3. Bradykinin (0.1, 0.3 and 1.0 nmol) injected into the placental arterial circulation produced an increase in placental perfusion pressure in all experiments. This effect of bradykinin was significantly inhibited by indomethacin (3 x 10(-7) M). 4. Captopril (10(-7) M) significantly potentiated the pressor effect of bradykinin on the human placental circulation (n = 6). This effect of captopril was reversed by indomethacin (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-response curves to angiotensin I (n = 6) were significantly displaced to the right by captopril in a concentration-dependent manner. 6. We suggest that the toxic effects of captopril on the foetus, rather than reflecting an inhibition of angiotensin II formation, may instead be related to a potentiation of the vasoconstrictor effect of bradykinin on the foetal placental circulation, thereby reducing blood flow and causing foetal damage. The reasons for this are discussed.(ABSTRACT TRUNCATED AT 250 WORDS)
de Moura
R
R
Departamento de Farmacologia e Psicobiologia, IB-HUPE, Universidade do Estado do Rio de Janeiro, Brasil.
Lopes
M A
MA
D000803:Angiotensin I / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology*; D001920:Bradykinin / Q000494:pharmacology*; D002216:Captopril / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D010920:Placenta / Q000098:blood supply / Q000187:drug effects*; D010925:Placental Function Tests; D011247:Pregnancy; D011453:Prostaglandins / Q000378:metabolism; D012039:Regional Blood Flow / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects
D011453:Prostaglandins; D000804:Angiotensin II; D000803:Angiotensin I; D002216:Captopril; D001920:Bradykinin; D007213:Indomethacin