Published Online
on November 25, 2002

A more recent version of this article appeared on January 1, 2003

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Submitted on June 3, 2002
Revised on July 29, 2002

Tissue-Specific Response to Interstitial Angiotensin II in Humans

Michael Boschmann^*; Jens Jordan; Frauke Adams; Niels-Juel Christensen; Jens Tank; Gabriele Franke; Mandy Stoffels; Arya M. Sharma; Friedrich C. Luft; and Susanne Klaus

From the German Institute of Human Nutrition (M.B., F.A., S.K.), Potsdam, Germany; Franz-Volhard Clinical Research Center and HELIOS Klinikum Berlin, Medical Faculty of the Charité, Humboldt-University (J.J., J.T., G.F., M.S., A.M.S., F.C.L.), Berlin, Germany; and the Department of Internal Medicine and Endocrinology, Herlev Hospital, University of Copenhagen (N.-J.C.), Denmark.

^* To whom correspondence should be addressed. E-mail: boschman{at}www.dife.de.

Abstract—Angiotensin II is synthesized locally in various tissues; however, the role of interstitial angiotensin II in the regulation of regional metabolism and tissue perfusion is not clear. We characterized the effect of interstially applied angiotensin II in skeletal muscle and subcutaneous adipose tissue of young, normal-weight, healthy subjects by using the microdialysis technique. Furthermore, we tested the hypothesis that the effect of interstitial angiotensin II is modulated by nitric oxide. Tissues were perfused with 0.01, 0.1, and 1 µmol/L angiotensin II in the presence of the L- or D-isomer of N^G-nitro-arginine-methyl ester (L- or D-NAME), the effective and noneffective isomer, respectively, for blocking nitric oxide synthase. Dialysate ethanol, glycerol, glucose, lactate, and pyruvate concentrations were measured to assess changes in blood flow (ethanol dilution technique), lipolysis, and glycolysis, respectively. Baseline blood flow and dialysate concentrations of the metabolites were similar with L- and D-NAME in both tissues. Blood flow and dialysate glucose and lactate did not change significantly in both tissues during perfusion with angiotensin II. Dialysate glycerol dose-dependently increased in adipose tissue (P<0.0438) but decreased in muscle (P<0.007). In muscle, dialysate pyruvate increased (P<0.0002), whereas lactate/pyruvate ratio decreased (P<0.001), both dose-dependently. All effects were similar with L- and D-NAME and could be reversed by nitroprusside. We conclude that in contrast to the profound hemodynamic effect of intravascular angiotensin II, interstitial angiotensin II has a minimal acute effect on blood flow in both tissues. However, interstitial angiotensin II modulates lipid and carbohydrate metabolism in a tissue specific fashion. Thus, the physiology of interstitial angiotensin II cannot be predicted from intravascular studies.

Key words: glucose • lactates • angiotensin II • microcirculation

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