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Aliskiren penetrates adipose and skeletal muscle tissue and reduces renin-angiotensin system activity in obese hypertensive patients

Item Type:Article
Title:Aliskiren penetrates adipose and skeletal muscle tissue and reduces renin-angiotensin system activity in obese hypertensive patients
Creators Name:Boschmann, M. and Nussberger, J. and Engeli, S. and Danser, A.H.J. and Yeh, C.M. and Prescott, M.F. and Dahlke, M. and Jordan, J.
Abstract:OBJECTIVE: In animals, the direct renin inhibitor aliskiren showed extensive tissue binding in the kidney and long-lasting renal effects. Aliskiren provides prolonged blood pressure-lowering effects following treatment discontinuation in patients. Therefore, we investigated whether aliskiren attains tissue concentrations sufficient to inhibit local renin-angiotensin system (RAS) activity in patients. METHODS: We included 10 hypertensive patients with abdominal adiposity in an open-label study. Following 1-2 weeks washout, patients received 2 weeks placebo, then 4 weeks aliskiren 300 mg once daily, followed by 4 weeks washout, and then 4 weeks amlodipine 5 mg once daily. Drug concentrations and RAS biomarkers were measured in interstitial fluid using microdialysis and in biopsies from abdominal subcutaneous adipose and skeletal muscle. RESULTS: We detected aliskiren in all compartments. After 4 weeks of treatment, microdialysate aliskiren concentrations (ng/ml) were 2.4 +/- 2.1 (adipose) and 7.1 +/- 4.2 (skeletal muscle), similar to plasma concentrations (8.4 +/- 4.4); tissue concentrations (ng/g) were 29.0 +/- 16.7 (adipose) and 107.3 +/- 68.6 (skeletal muscle). Eight weeks after discontinuation, aliskiren was measurable in tissue biopsies but not in plasma or in interstitial fluid. Pooled microdialysate samples from two sets of four patients suggested reduction in tissue angiotensin II with aliskiren but not with amlodipine. CONCLUSION: In obese hypertensive patients, aliskiren penetrates adipose and skeletal muscle tissue at levels that are apparently sufficient to reduce tissue RAS activity. Furthermore, tissue binding may contribute to aliskiren's prolonged blood pressure-lowering effect following discontinuation.
Keywords:Adipose Tissue, Adipose Tissue, Direct Renin Inhibitor, Metabolic Syndrome, Microdialysis, Obesity
Source:Journal of Hypertension
Publisher:Lippincott Williams & Wilkins
Page Range:561-566
Date:March 2012
Official Publication:https://doi.org/10.1097/HJH.0b013e32834f6b43
PubMed:View item in PubMed

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