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Local NOS inhibition impairs vascular and metabolic actions of insulin in rat hindleg muscle in vivo


Bradley, EA and Richards, SM and Keske, MA and Rattigan, S, Local NOS inhibition impairs vascular and metabolic actions of insulin in rat hindleg muscle in vivo, American Journal of Physiology: Endocrinology and Metabolism, 305, (6) pp. E745-E750. ISSN 0193-1849 (2013) [Refereed Article]

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Copyright 2013 3 the American Physiological Society

DOI: doi:10.1152/ajpendo.00289.2013


Insulin stimulates microvascular recruitment in skeletal muscle, and this vascular action augments muscle glucose disposal by ∼40%. The aim of the current study was to determine the contribution of local nitric oxide synthase (NOS) to the vascular actions of insulin in muscle. Hooded Wistar rats were infused with the NOS inhibitor N(ω)-nitro-L-arginine methylester (L-NAME, 10 μM) retrogradely via the epigastric artery in one leg during a systemic hyperinsulinemic-euglycemic clamp (3 mU·min(-1)·kg(-1) × 60 min) or saline infusion. Femoral artery blood flow, microvascular blood flow (assessed from 1-methylxanthine metabolism), and muscle glucose uptake (2-deoxyglucose uptake) were measured in both legs. Local L-NAME infusion did not have any systemic actions on blood pressure or heart rate. Local L-NAME blocked insulin-stimulated changes in femoral artery blood flow (84%, P < 0.05) and microvascular recruitment (98%, P < 0.05), and partially blocked insulin-mediated glucose uptake in muscle (reduced by 34%, P < 0.05). L-NAME alone did not have any metabolic effects in the hindleg. We conclude that insulin-mediated microvascular recruitment is dependent on local activation of NOS in muscle and that this action is important for insulin's metabolic actions.

Item Details

Item Type:Refereed Article
Keywords:muscle blood flow; microvascular blood flow; hyperinsulinemic euglycemic clamp; nitric oxide; nitric oxide synthase
Research Division:Biomedical and Clinical Sciences
Research Group:Clinical sciences
Research Field:Endocrinology
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Bradley, EA (Miss Eloise Bradley)
UTAS Author:Richards, SM (Dr Stephen Richards)
UTAS Author:Keske, MA (Dr Michelle Keske)
UTAS Author:Rattigan, S (Professor Stephen Rattigan)
ID Code:87525
Year Published:2013
Web of Science® Times Cited:28
Deposited By:Menzies Institute for Medical Research
Deposited On:2013-11-21
Last Modified:2017-11-02

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