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Achieving the goal of optimised renin system suppression: preclinical experience with a direct renin inhibitor

Item Type:Article
Title:Achieving the goal of optimised renin system suppression: preclinical experience with a direct renin inhibitor
Creators Name:Luft, F.C.
Abstract:Aliskiren is the first orally available direct renin inhibitor and is a highly potent and specific inhibitor of human renin.The high specificity for human renin has resulted in considerable challenges in utilising animal models in preclinical studies. Both marmoset and spontaneously hypertensive rat models demonstrate the safety and efficacy of aliskiren in reducing blood pressure, although both models have drawbacks.The former are difficult to study, while the latter feature a renin that is less amenable to inhibition by a human-reninspecific drug. However, a double transgenic rat (dTGR) model has been shown to be extremely valuable in preclinical studies of aliskiren.These rats are designed to express genes for human renin and angiotensinogen. Preclinical studies in dTGR demonstrate the efficacy and safety of aliskiren, both as monotherapy and in combination with ACE inhibitors and ARBs in the treatment of hypertension. Direct renin inhibition with aliskiren improves kidney function and reduces left ventricular hypertrophy, and may have the potential to provide end-organ protection.
Keywords:Aliskiren, Direct renin, Inhibitor, Hypertension, Animal models, Preclinical studies
Source:Journal of the Renin Angiotensin Aldosterone System
ISSN:1470-3203
Publisher:JRAAS Ltd. (U.K.)
Volume:7
Number:Suppl 2
Page Range:S12-S15
Date:December 2006
Official Publication:https://doi.org/10.3317/jraas.2006.032

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