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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 RattiganInsulin 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.
History
Publication title
American Journal of Physiology: Endocrinology and MetabolismVolume
305Issue
6Pagination
E745-E750ISSN
0193-1849Department/School
Menzies Institute for Medical ResearchPublisher
Amer Physiological SocPlace of publication
9650 Rockville Pike, Bethesda, USA, Md, 20814Rights statement
Copyright 2013 3 the American Physiological SocietyRepository Status
- Restricted