Effect of angiotensin-converting-enzyme inhibition on bradykinin metabolism by vascular endothelial cells

• Published in: The American journal of physiology Vol. 264; no. 5 Pt 2; p. H1493
• Main Authors: Gräfe, M, Bossaller, C, Graf, K, Auch-Schwelk, W, Baumgarten, C R, Hildebrandt, A, Fleck, E
• Format: Journal Article
• Language: English
• Published: United States 01.05.1993
• Subjects: Angiotensin-Converting Enzyme Inhibitors - pharmacology; Bradykinin - metabolism; Cells, Cultured; Dipeptides - pharmacology; Endothelium, Vascular - cytology; Endothelium, Vascular - metabolism; Half-Life; Humans; Lisinopril; Osmolar Concentration; Radioimmunoassay; Ramipril - analogs & derivatives; Ramipril - pharmacology; Time Factors
• ISSN: 0002-9513; 2163-5773
• DOI: 10.1152/ajpheart.1993.264.5.h1493

The degradation of bradykinin by angiotensin-converting-enzyme (ACE) activity in cultured human endothelial cells was studied by direct measurement of bradykinin and by its effect on the release of endothelium-derived relaxing factors. The half-life of exogenous bradykinin (10,000 pg/ml) was calculated from the decay of the bradykinin concentration as 46 +/- 2 min in cell monolayers, 133 +/- 15 min in conditioned medium, and 24 +/- 2 min in homogenates. Most of the bradykinin-degrading activity in cell monolayers could be inhibited in a concentration-dependent manner by the ACE inhibitors lisinopril, ramiprilat, and captopril. Bradykinin-degrading activity was released into the culture medium containing one-fourth of the bradykinin-degrading activity found in the presence of cell monolayers. In cell homogenates higher unspecific bradykinin-degrading activities were present. The functional consequence of bradykinin degradation was demonstrated by the potentiating effect of ramiprilat on the generation of endothelium-derived relaxing factors nitric oxide and prostacyclin from endothelial cells. The study supports the concept of increased vasodilatory effects of bradykinin during ACE inhibition.