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Activation of AMP-Activated Protein Kinase by 5-Aminoimidazole-4-Carboxamide-1-β-D-Ribofuranoside in the Muscle Microcirculation Increases Nitric Oxide Synthesis and Microvascular Perfusion

Citation

Bradley, EA and Eringa, EC and Stehouwer, CDA and Korstjens, I and van Nieuw Amerongen, GP and Musters, R and Sipkema, P and Clark, MG and Rattigan, S, Activation of AMP-Activated Protein Kinase by 5-Aminoimidazole-4-Carboxamide-1-β-D-Ribofuranoside in the Muscle Microcirculation Increases Nitric Oxide Synthesis and Microvascular Perfusion, Arteriosclerosis, Thrombosis, and Vascular Biology, 30, (6) pp. 1137-1142. ISSN 1079-5642 (2010) [Refereed Article]


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Copyright Statement

Copyright © 2010 American Heart Association.

DOI: doi:10.1161/ATVBAHA.110.204404

Abstract

Objective—To investigate the effects of activation of the AMP-activated protein kinase (AMPK) on muscle perfusion and to elucidate the mechanisms involved. Methods and Results—In a combined approach, we studied the vasoactive actions of AMPK activator by 5-aminoimidazole-4-carboxamide-1--D-ribofuranoside (AICAR) on rat cremaster muscle resistance arteries (100 m) ex vivo and on microvascular perfusion in the rat hindlimb in vivo. In isolated resistance arteries, AICAR increased Thr172 phosphorylation of AMPK in arteriolar endothelium, which was predominantly located in microvascular endothelium. AICAR induced vasodilation (194% at 2 mmol/L, P0.01), which was abolished by endothelium removal, inhibition of NO synthase (with N-nitro-L-arginine), or AMPK (with compound C). Smooth muscle sensitivity to NO, determined by studying the effects of the NO donor S-nitroso-N-acetylpenicillamine (SNAP), was not affected by AICAR except at the highest dose. AICAR increased endothelial nitric oxide synthase activity, as indicated by Ser1177 phosphorylation. In vivo, infusion of AICAR markedly increased muscle microvascular blood volume (60%, P0.05), as was evidenced by contrast-enhanced ultrasound, without effects on blood pressure, femoral blood flow, or hind leg glucose uptake. Conclusion—Activation of AMPK by AICAR activates endothelial nitric oxide synthase in arteriolar endothelium by increasing its Ser1177 phosphorylation, which leads to vasodilation of resistance arteries and recruitment of microvascular perfusion in muscle.

Item Details

Item Type:Refereed Article
Keywords:AICAR; AMPK; microcirculation; muscle; hemodynamics
Research Division:Medical and Health Sciences
Research Group:Cardiorespiratory Medicine and Haematology
Research Field:Cardiology (incl. Cardiovascular Diseases)
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Diabetes
Author:Bradley, EA (Miss Eloise Bradley)
Author:Clark, MG (Professor Michael Clark)
Author:Rattigan, S (Professor Stephen Rattigan)
ID Code:64813
Year Published:2010
Web of Science® Times Cited:47
Deposited By:Menzies Institute for Medical Research
Deposited On:2010-09-02
Last Modified:2011-04-29
Downloads:0

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