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

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.

• Authors: Stefan Engeli, Marcus May, Juerg Nussberger, A H Jan Danser, William P Dole, Margaret F Prescott, Marion Dahlke, Sylvie Stitah, Parasar Pal, Michael Boschmann, Jens Jordan
• Journal: Journal of the American Society of Hypertension : JASH (J Am Soc Hypertens) Vol. 11 Issue 8 Pg. 488-497 (Aug 2017) ISSN: 1878-7436 [Electronic] United States
• PMID: 28666704 (Publication Type: Comparative Study, Journal Article, Randomized Controlled Trial)
• Copyright: Copyright © 2017 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

Chemical References

• Amides
• Antihypertensive Agents
• Blood Glucose
• Fumarates
• Insulin
• Angiotensin II
• Amlodipine
• aliskiren
• Renin
• Glucose

Topics

• Adipose Tissue (drug effects, metabolism)
• Adult
• Amides (pharmacology, therapeutic use)
• Amlodipine (pharmacology, therapeutic use)
• Angiotensin II (metabolism)
• Antihypertensive Agents (pharmacology, therapeutic use)
• Blood Glucose (drug effects)
• Double-Blind Method
• Female
• Fumarates (pharmacology, therapeutic use)
• Glucose (metabolism)
• Humans
• Hypertension (blood, drug therapy, etiology, metabolism)
• Insulin (blood)
• Lipolysis (drug effects)
• Male
• Microdialysis
• Middle Aged
• Muscle, Skeletal (drug effects, metabolism)
• Obesity (blood, complications, drug therapy, metabolism)
• Renin (antagonists & inhibitors)
• Renin-Angiotensin System (drug effects)