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

journal contribution
posted on 2023-05-17, 20:38 authored by Bradley, EA, Stephen RichardsStephen Richards, Michelle Keske, Stephen RattiganStephen Rattigan
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.


Publication title

American Journal of Physiology: Endocrinology and Metabolism










Menzies Institute for Medical Research


Amer Physiological Soc

Place of publication

9650 Rockville Pike, Bethesda, USA, Md, 20814

Rights statement

Copyright 2013 3 the American Physiological Society

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  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified