Intra-arterial AICA-riboside administration induces NO-dependent vasodilation in vivo in human skeletal muscle

• In animal models, administration of the adenosine analog AICA-riboside has shown beneficial effects on ischemia-reperfusion injury and glucose homeostasis. The vascular and/or metabolic effects of AICA-riboside administration in humans remain to be established. AICA-riboside was infused intra-arterially in four different dosages up to 8 mg·min-1·dl-1 in 24 healthy subjects. Forearm blood flow (FBF) and glucose uptake and plasma glucose, free fatty acid, and AICA-riboside concentrations were assessed. We also combined AICAriboside infusion (2 mg·min-1·dl -1) with the intra-arterial administration of the adenosine receptor antagonist caffeine (90 μg·min-1·dl-1; n = 6) and with the endothelial NO synthase inhibitor L-NMMA (0.4 mg·min-1·dl-1; n = 6). Additional in vitro experiments were performed to explain our in vivo effects of AICA-riboside in humans. AICA-riboside increased FBF dose dependently from 2.0 ± 0.2 to 13.2 ± 1.9 ml·min-1·dl-1 maximally (P < 0.05 for all dosages). The latter was not reduced by caffeine administration but was significantly attenuated by L-NMMA infusion. Despite high plasma AICA-riboside concentrations, forearm glucose uptake did not change. In vitro experiments showed rapid uptake of AICA-riboside by the equilibrative nucleoside transporter in erythrocytes and subsequent phosphorylation to AICA-ribotide. We conclude that AICA-riboside induces a potent vasodilator response in humans that is mediated by NO. Despite high local plasma concentrations, AICA-riboside does not increase skeletal muscle glucose uptake. Copyright © 2009 the American Physiological Society.

Nyckelord

5-Aminoimidazole-4-carboxamide

Forearm blood flow

Forearm glucose uptake

Nitric oxide

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