TY - JOUR
T1 - Intra-arterial AICA-riboside administration induces NO-dependent vasodilation in vivo in human skeletal muscle.
AU - Bosselaar, M.
AU - Boon, H.
AU - van Loon, L.J.
AU - Broek, P.H.
AU - Smits, P.
AU - Tack, C.
PY - 2009/1/1
Y1 - 2009/1/1
N2 - 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.
AB - 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.
U2 - 10.1152/ajpendo.00141.2009
DO - 10.1152/ajpendo.00141.2009
M3 - Article
C2 - 19602584
SN - 0193-1849
VL - 297
SP - E759-E766
JO - American Journal of Physiology : Endocrinology and Metabolism
JF - American Journal of Physiology : Endocrinology and Metabolism
IS - 3
ER -