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

M. Bosselaar, H. Boon, L.J. van Loon, P.H. Broek, P. Smits, C. Tack

    Research output: Contribution to journalArticleAcademicpeer-review

    Abstract

    Aims: In animal models, administration of the adenosine analogue 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. Methods: AICA-riboside was infused intra-arterially in 4 different dosages up to 8 mg/min/dl 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/min/dl) with the intra-arterial administration of the adenosine receptor antagonist caffeine (90 microg/min/dl, n=6) and with the endothelial NO-synthase inhibitor L-NMMA (0.4 mg/min/dl, n=6). Additional in vitro experiments were performed to explain our in vivo effects of AICA-riboside in humans. Results: AICA-riboside increased FBF dose-dependently from 2.0+/-0.2 to 13.2+/-1.9 ml/min/dl maximally (P<0.05 for all dosages). The latter was not reduced by caffeine administration, but 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 (ZMP). Conclusions: AICA-riboside induces a potent vasodilator response in humans, which is mediated by NO. Despite high local plasma concentrations, AICA-riboside does not increase skeletal muscle glucose uptake. Key words: human in vivo, AICA-riboside, NO, forearm blood flow, forearm glucose uptake.
    Original languageEnglish
    Pages (from-to)E759-E766
    JournalAmerican Journal of Physiology : Endocrinology and Metabolism
    Volume297
    Issue number3
    DOIs
    Publication statusPublished - 1 Jan 2009

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