In vitro comparison of bradykinin degradation by aliskiren, a renin inhibitor, and an inhibitor of angiotensin-converting enzyme.
INTRODUCTION
Angiotensin-converting enzyme (ACE) inhibitors cause angioedema due to diminished degradation of bradykinin. Angiotensin receptor blockers may occasionally cause angioedema but the mechanism is unknown, and are generally considered safe, even in those who have reacted to ACE inhibitors. We determined whether aliskiren, a renin inhibitor, has an effect on the rate of bradykinin degradation.


METHODS
The ability of renin to metabolize bradykinin was studied and the rate of bradykinin degradation compared in the presence or absence of aliskiren. Enalapril, a known ACE inhibitor that causes angioedema served as positive control.


RESULTS
Renin was unable to digest bradykinin, indicating that a renin inhibitor is unlikely to affect the rate of bradykinin degradation. In a plasma system, aliskiren had no effect on the rate of bradykinin degradation while enalapril inhibited it appreciably. An inhibitory effect of aliskiren on the rate of bradykinin degradation by human pulmonary endothelial cells was observed, estimated to be about 5% of that of enalapril.


CONCLUSION
Aliskiren has no effect upon the rate of bradykinin degradation in plasma and a minimal effect employing vascular endothelial cells. The latter suggests inhibition of a non-renin enzyme that is a minor contributor to bradykinin degradation.
['Joseph|Kusumam|K|', 'Tholanikunnel|Tracy E|TE|', 'Kaplan|Allen P|AP|']
D015097:3-Mercaptopropionic Acid D000577:Amides D000806:Angiotensin-Converting Enzyme Inhibitors D001920:Bradykinin D042783:Endothelial Cells D005650:Fumarates D006801:Humans D007703:Peptidyl-Dipeptidase A D011651:Pulmonary Artery D012083:Renin
bradykinin aliskiren Angioedema ACE inhibitor enalapril