Systemic and tissue-specific effects of aliskiren on the RAAS and carbohydrate/lipid metabolism in obese patients with hypertension

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Item Type:	Article
Title:	Systemic and tissue-specific effects of aliskiren on the RAAS and carbohydrate/lipid metabolism in obese patients with hypertension
Creators Name:	Engeli, S., May, M., Nussberger, J., Danser, A.H.J., Dole, W.P., Prescott, M.F., Dahlke, M., Stitah, S., Pal, P., Boschmann, M. and Jordan, J.
Abstract:	Aliskiren penetrates adipose and skeletal muscle in hypertensive patients with abdominal obesity and reduces renin-angiotensin-aldosterone system activity. After discontinuation, blood pressure-lowering effects are observed possibly through drug-tissue binding. We performed microdialysis evaluation of adipose tissue and skeletal muscle before and during an insulin-modified frequently sampled intravenous glucose tolerance test (IM-FSIGT). Aliskiren 300 mg (n = 8) or amlodipine 5 mg (n = 8) once daily were administered during a 12-week randomized treatment period. Aliskiren elicited variable changes in median interstitial angiotensin II (Ang II) in adipose (2.60-1.30 fmol/mL) and skeletal muscle (2.23-0.68 fmol/mL); amlodipine tended to increase adipose and skeletal muscle Ang II (P = .066 for skeletal muscle treatment difference). Glucose/insulin increased median plasma Ang II 1 hour after glucose injection (1.04-2.50 fmol/mL; P = .001), which was markedly attenuated by aliskiren but not amlodipine. Aliskiren increased glucose disposition index (P = .012) and tended to increase acute insulin response to glucose (P = .067). Fasting adipose glycerol (-17%; P = .064) and fasting muscle glucose dialysate (-17%; P = .025) were decreased by aliskiren but not amlodipine. In summary, aliskiren decreased Ang II production in response to glucose/insulin stimulus and elicited metabolic effects in adipose and skeletal muscle suggestive of increased whole-body glucose utilization.
Keywords:	Adipose Tissue, Amlodipine, Angiotensin II, Insulin Sensitivity, Microdialysis, Obesity, Plasma Renin Activity, Skeletal Muscle
Source:	Journal of the American Society of Hypertension
ISSN:	1933-1711
Publisher:	Elsevier
Volume:	11
Number:	8
Page Range:	488-497
Date:	August 2017
Official Publication:	https://doi.org/10.1016/j.jash.2017.06.002
PubMed:	View item in PubMed

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