1. Intra-arterial AICA-riboside administration induces NO-dependent vasodilation in vivo in human skeletal muscle.
- Author
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Bosselaar M, Boon H, van Loon LJ, van den Broek PH, Smits P, and Tack CJ
- Subjects
- Adult, Aminoimidazole Carboxamide administration & dosage, Aminoimidazole Carboxamide pharmacology, Brachial Artery drug effects, Brachial Artery physiology, Caffeine administration & dosage, Cells, Cultured, Enzyme Inhibitors administration & dosage, Female, Forearm blood supply, Hemodynamics drug effects, Humans, Injections, Intra-Arterial, Male, Muscle, Skeletal drug effects, NG-Nitroarginine Methyl Ester administration & dosage, Regional Blood Flow drug effects, Ribonucleosides administration & dosage, Young Adult, Aminoimidazole Carboxamide analogs & derivatives, Muscle, Skeletal blood supply, Nitric Oxide pharmacology, Ribonucleosides pharmacology, Vasodilation drug effects
- Abstract
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 x min(-1) x 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 AICA-riboside infusion (2 mg x min(-1) x dl(-1)) with the intra-arterial administration of the adenosine receptor antagonist caffeine (90 microg x min(-1) x dl(-1); n = 6) and with the endothelial NO synthase inhibitor l-NMMA (0.4 mg x min(-1) x 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 x min(-1) x 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.
- Published
- 2009
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