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.
Gräfe
M
M
Department of Cardiology, German Heart Institute, Berlin.
Bossaller
C
C
Graf
K
K
Auch-Schwelk
W
W
Baumgarten
C R
CR
Hildebrandt
A
A
Fleck
E
E
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