Effect of angiotensin-converting-enzyme inhibition on bradykinin metabolism by vascular endothelial cells.
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.
Department of Cardiology, German Heart Institute, Berlin.
M
M
Gräfe
C
C
Bossaller
K
K
Graf
W
W
Auch-Schwelk
C R
CR
Baumgarten
A
A
Hildebrandt
E
E
Fleck
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D001920:Bradykinin / Q000378:metabolism*; D002478:Cells, Cultured; D004151:Dipeptides / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D006207:Half-Life; D006801:Humans; D017706:Lisinopril; D009994:Osmolar Concentration; D011863:Radioimmunoassay; D017257:Ramipril / Q000031:analogs & derivatives / Q000494:pharmacology; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D004151:Dipeptides; C052549:ramiprilat; D017706:Lisinopril; D017257:Ramipril; D001920:Bradykinin