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Am J Physiol Regul Integr Comp Physiol 290: R219-R223, 2006. First published August 18, 2005; doi:10.1152/ajpregu.00341.2005
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APPETITE, OBESITY, DIGESTION, AND METABOLISM

Influences of AT1 receptor blockade on tissue metabolism in obese men

Michael Boschmann,1 Stefan Engeli,1 Frauke Adams,1 Gabriele Franke,1 Friedrich C. Luft,1 Arya M. Sharma,2 and Jens Jordan1

1Franz-Volhard Clinical Research Center, Charité Campus Buch and HELIOS Klinikum, Berlin, Germany; and 2Department of Medicine, McMaster University, Hamilton General Hospital, Hamilton, Ontario, Canada

Submitted 12 May 2005 ; accepted in final form 12 August 2005

ANG II applied to the interstitial space influences carbohydrate and lipid metabolism in a tissue-specific fashion. Thus endogenous ANG II may have a tonic effect on tissue metabolism that could be reversed with ANG II type 1 (AT1) receptor blockade, particularly during adrenergic stimulation. We studied 14 obese men. They were treated for 10 days with the AT1 receptor blocker irbesartan or with placebo in a double-blind and crossover fashion. At the end of each treatment period, we assessed skeletal muscle and adipose tissue metabolism using the microdialysis technique. The ethanol dilution technique was applied to follow changes in tissue blood flow. Measurements were obtained at baseline and during application of incremental isoproterenol concentrations through the microdialysis catheter. Blood pressure decreased from 133 ± 3/84 ± 3 to 128 ± 3/79 ± 2 mmHg for systolic and diastolic blood, respectively (P = 0.02 and 0.006, respectively) with AT1 receptor blockade. Isoproterenol perfusion caused a dose-dependent increase in dialysate glycerol in adipose tissue and in skeletal muscle. Irbesartan slightly reduced the isoproterenol-induced glycerol response in adipose tissue (P < 0.05 by ANOVA). Ethanol ratio, interstitial glucose supply, and lactate production in adipose tissue and skeletal muscle were similar with placebo and irbesartan. We conclude that AT1 receptor blockade in obese men does not reveal a major tonic ANG II effect on interstitial glucose supply, lipolysis, or glycolysis in skeletal muscle, either at rest or during {beta}-adrenergic stimulation. Endogeneous ANG II may slightly increase adipose tissue lipolysis. The mechanism may promote the redistribution of triglycerides from adipose tissue toward other organs.

adipose tissue; angiotensin II; insulin


Address for reprint requests and other correspondence: J. Jordan, Franz Volhard Clinical Research Center, Haus 129, Charité Campus Buch, Wiltbergstr. 50, 13125 Berlin, Germany (e-mail: jordan{at}fvk.charite-buch.de)






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