EFFECT OF ANGIOTENSIN-CONVERTING-ENZYME INHIBITION ON BRADYKININ METABOLISM BY VASCULAR ENDOTHELIAL-CELLS

The degradation of bradykinin by angiotensin-converting-enzyme (ACE) a ctivity in cultured human endothelial cells was studied by direct meas urement of bradykinin and by its effect on the release of endothelium- derived relaxing factors. The half-life of exogenous bradykinin (10,00 0 pg/ml) was calculated from the decay of the bradykinin concentration as 46 +/- 2 min in cell monolayers, 133 +/- 15 min in conditioned med ium, and 24 +/- 2 min in homogenates. Most of the bradykinin-degrading activity in cell monolayers could be inhibited in a concentration-dep endent manner by the ACE inhibitors lisinopril, ramiprilat, and captop ril. Bradykinin-degrading activity was released into the culture mediu m containing one-fourth of the bradykinin-degrading activity found in the presence of cell monolayers. In cell homogenates, higher unspecifi c bradykinin-degrading activities were present. The functional consequ ence of bradykinin degradation was demonstrated by the potentiating ef fect of ramiprilat on the generation of endothelium-derived relaxing f actors nitric oxide and prostacyclin from endothelial cells. The study supports the concept of increased vasodilatory effects of bradykinin during ACE inhibition.