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.