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Systemic and tissue-specific effects of aliskiren on the RAAS and carbohydrate/Pipid metabolism in obeses hypertensives

Engeli, S. and May, M. and Nussberger, J. and Danser, A.H.J. and Dole, W.P. and Prescott, M.F. and Dahlke, M. and Stitah, S. and Pal, P. and Boschmann, M. and Jordan, J. (2017) Systemic and tissue-specific effects of aliskiren on the RAAS and carbohydrate/Pipid metabolism in obeses hypertensives. Journal of the American Society of Hypertension, 11 (8), pp. 488-497. DOI: 10.1016/j.jash.2017.06.002 ISSN 1933-1711

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Abstract

Aliskiren penetrates adipose and skeletal muscle in hypertensive patients with abdominal obesity and reduces renin–angio- tensin–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 mus- cle 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.

Item URL in elib:https://elib.dlr.de/118787/
Document Type:Article
Title:Systemic and tissue-specific effects of aliskiren on the RAAS and carbohydrate/Pipid metabolism in obeses hypertensives
Authors:
AuthorsInstitution or Email of AuthorsAuthors ORCID iD
Engeli, S.Hannover Medical School, Hannover, GermanyUNSPECIFIED
May, M.Hannover Medical School, Hannover, GermanyUNSPECIFIED
Nussberger, J.Universitaire Vaudois, Lausanne, SwitzerlandUNSPECIFIED
Danser, A.H.J.Erasmus Medical Center, Rotterdam NetherlandsUNSPECIFIED
Dole, W.P.Novartis Pharmaceuticals Corporation, East Hannover, NJ, USAUNSPECIFIED
Prescott, M.F.Novartis Pharmaceuticals Corporation, East Hannover, NJ, USAUNSPECIFIED
Dahlke, M.Novartis Pharma AG, Basel, SwitzerlandUNSPECIFIED
Stitah, S.Novartis Pharma AG, Basel, SwitzerlandUNSPECIFIED
Pal, P.Novartis Healthcare Private Limited, Hyderabad, IndiaUNSPECIFIED
Boschmann, M.Charite, BerlinUNSPECIFIED
Jordan, J.Institute of Aerospace Medicine, German Aerospace Center (DLR), Cologne, Germany.UNSPECIFIED
Date:2017
Journal or Publication Title:Journal of the American Society of Hypertension
Refereed publication:Yes
Open Access:No
Gold Open Access:No
In SCOPUS:Yes
In ISI Web of Science:Yes
Volume:11
DOI :10.1016/j.jash.2017.06.002
Page Range:pp. 488-497
ISSN:1933-1711
Status:Published
Keywords:Adipose tissue, amlodipine, angiotensinII Insulin sensitivity, microdialysis, obesity, Plasma renin activity skeletal muscle
HGF - Research field:Aeronautics, Space and Transport
HGF - Program:Space
HGF - Program Themes:Research under Space Conditions
DLR - Research area:Raumfahrt
DLR - Program:R FR - Forschung unter Weltraumbedingungen
DLR - Research theme (Project):R - Projekt :envihab
Location: Köln-Porz
Institutes and Institutions:Institute of Aerospace Medicine > Leitungsbereich ME
Deposited By: Jackman, Sabine
Deposited On:06 Feb 2018 11:09
Last Modified:06 Feb 2018 11:09

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