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Opposing Effects of Angiotensin II on Muscle and Renal Blood Flow under Euglycemic Conditions

Department of Internal Medicine, Ruperto-Carola University, Heidelberg, Germany.

Correspondence to Dr. Eberhard Ritz, Division of Nephrology, Department of Internal Medicine, Ruperto-Carola University, Bergheimerstrasse 56 a, 69115 Heidelberg, Germany. Phone: 49-06221-911-20; Fax: 49-06221-16-24-76; E-mail: prof.e.ritz{at}t-online.de

Abstract. Angiotensin II (Ang II) enhances insulin sensitivity in humans, and this is associated with a paradoxical increase in skeletal muscle blood flow. It is unclear whether these effects are mediated via subtype 1 receptors of Ang II, because these receptors are thought to mediate vasoconstriction. Insulin-stimulated glucose uptake (euglycemic clamp technique) and leg muscle blood flow (plethysmography) were measured in nine healthy male volunteers (mean age, 24 ± 2 yr) on three occasions using a double-blind, placebo-controlled study design. The subjects were allocated in random order to (1) placebo premedication per os plus placebo infusion, (2) placebo premedication per os plus infusion of 5 ng Ang II/kg per min, and (3) premedication with 300 mg of the angiotensin II-1-receptor antagonist irbesartan per os plus infusion of 5 ng Ang II/kg per min. In addition, GFR and effective renal plasma flow were assessed using the steady-state inulin- and paraaminohippurate clearance. Insulin sensitivity (i.e., M value) and muscle blood flow after infusion of Ang II (9.3 ± 1.8 mg/kg per min; 17.7 ± 2.1 ml/100 g per min) were significantly higher than after placebo infusion (7.2 ± 1.6 mg/kg per min, P < 0.02; 13.5 ± 1.8 ml/100 g per min, P < 0.01). In contrast, after premedication with irbesartan, they were not significantly different (7.5 ± 1.7 mg/kg per min; 14.3 ± 1.9 ml/100 g per min) as compared with placebo infusion. Mean GFR and effective renal plasma flow were significantly lower (P < 0.01), and renal vascular resistance was significantly higher (P < 0.01) with Ang II infusion as compared with the placebo infusion study. Premedication with irbesartan almost completely blocked the vasoconstrictive effect of Ang II on renal vasculature. Under hyperinsulinemic euglycemic conditions, infusion of Ang II has opposing effects on regional arterial blood flow, i.e., an increase in skeletal muscle blood flow, but vasoconstriction of renal vasculature. Both effects are antagonized by blockade of subtype 1 Ang II receptors.

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Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673