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

Details

Serval ID
serval:BIB_82F1124E75DA
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Systemic and tissue-specific effects of aliskiren on the RAAS and carbohydrate/lipid metabolism in obese patients with hypertension.
Journal
Journal of the American Society of Hypertension
Author(s)
Engeli S., May M., Nussberger J., Danser AHJ, Dole W.P., Prescott M.F., Dahlke M., Stitah S., Pal P., Boschmann M., Jordan J.
ISSN
1878-7436 (Electronic)
ISSN-L
1878-7436
Publication state
Published
Issued date
08/2017
Peer-reviewed
Oui
Volume
11
Number
8
Pages
488-497
Language
english
Notes
Publication types: Comparative Study ; Journal Article ; Randomized Controlled Trial
Publication Status: ppublish
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/drug effects, Adipose Tissue/metabolism, Adult, Amides/pharmacology, Amides/therapeutic use, Amlodipine/pharmacology, Amlodipine/therapeutic use, Angiotensin II/metabolism, Antihypertensive Agents/pharmacology, Antihypertensive Agents/therapeutic use, Blood Glucose/drug effects, Double-Blind Method, Female, Fumarates/pharmacology, Fumarates/therapeutic use, Glucose/metabolism, Humans, Hypertension/blood, Hypertension/drug therapy, Hypertension/etiology, Hypertension/metabolism, Insulin/blood, Lipolysis/drug effects, Male, Microdialysis, Middle Aged, Muscle, Skeletal/drug effects, Muscle, Skeletal/metabolism, Obesity/blood, Obesity/complications, Obesity/drug therapy, Obesity/metabolism, Renin/antagonists & inhibitors, Renin-Angiotensin System/drug effects, Adipose tissue, amlodipine, angiotensin II, insulin sensitivity, microdialysis, obesity, plasma renin activity, skeletal muscle
Pubmed
Web of science
Create date
28/07/2017 12:37
Last modification date
20/08/2019 14:42
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