In vitro comparison of bradykinin degradation by aliskiren, a renin inhibitor, and an inhibitor of angiotensin-converting enzyme.

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Joseph K, Tholanikunnel TE, Kaplan AP

In vitro comparison of bradykinin degradation by aliskiren, a renin inhibitor, and an inhibitor of angiotensin-converting enzyme.

J Renin Angiotensin Aldosterone Syst. 2015 Jun;16(2):321-7. doi: 10.1177/1470320313491997. Epub 2013 Jun 13.

PubMed ID

23764715 [ View in PubMed

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Abstract

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.

DrugBank Data that Cites this Article

Pharmaco-metabolomics

Drug	Drug Groups	Metabolite	Change	Description
Aliskiren	Approved Investigational	cardiac bradykinin	increased	Aliskiren increases the level of cardiac bradykinin in the blood