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Local NOS inhibition impairs vascular and metabolic actions of insulin in rat hindleg muscle in vivo
journal contribution
posted on 2013-09-15, 00:00 authored by E A Bradley, S M Richards, Michelle KeskeMichelle Keske, S 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
Journal
American journal of physiology: endocrinology and metabolismVolume
305Issue
6Pagination
E745 - E750Publisher
American Physiological SocietyLocation
Bethesda, Md.Publisher DOI
ISSN
0193-1849eISSN
1522-1555Language
engPublication classification
C Journal article; C1.1 Refereed article in a scholarly journalCopyright notice
2013, American Physiological SocietyUsage metrics
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muscle blood flowmicrovascular blood flowhyperinsulinemic-euglycemic clampnitric oxidenitric oxide synthaseAnimalsBlood Flow VelocityBlood GlucoseBlood PressureEnzyme InhibitorsFemoral ArteryHeart RateHindlimbInsulinMaleMuscle, SkeletalNG-Nitroarginine Methyl EsterRatsRats, WistarRegional Blood FlowScience & TechnologyLife Sciences & BiomedicineEndocrinology & MetabolismPhysiologyNITRIC-OXIDE SYNTHASEMEDIATED CAPILLARY RECRUITMENTHUMAN FOREARM MUSCLESKELETAL-MUSCLEMICROVASCULAR RECRUITMENTGLUCOSE-UPTAKEENDOTHELIAL-CELLSSTIMULATED PRODUCTIONBLOOD-FLOWMIXED MEAL
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