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

Version 2 2024-06-04, 10:47
Version 1 2017-03-21, 17:07
journal contribution
posted on 2024-06-04, 10:47 authored by EA Bradley, SM Richards, Michelle KeskeMichelle Keske, S 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.

History

Journal

American journal of physiology: endocrinology and metabolism

Volume

305

Pagination

E745-E750

Location

Bethesda, Md.

ISSN

0193-1849

eISSN

1522-1555

Language

eng

Publication classification

C Journal article, C1.1 Refereed article in a scholarly journal

Copyright notice

2013, American Physiological Society

Issue

6

Publisher

American Physiological Society