title: Local NOS inhibition impairs vascular and metabolic actions of insulin in rat hindleg muscle in vivo.
abstract: 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.
authors.affiliation: Menzies Research Institute Tasmania, University of Tasmania, Hobart, Australia.
authors.forename: Eloise A
authors.initials: EA
authors.lastname: Bradley
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Richards
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Keske
authors.forename: Stephen
authors.initials: S
authors.lastname: Rattigan
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005263:Femoral Artery / Q000187:drug effects / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects; D006614:Hindlimb / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects
chemical_list: D001786:Blood Glucose; D004791:Enzyme Inhibitors; D007328:Insulin; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester
keywords: hyperinsulinemic-euglycemic clamp; microvascular blood flow; muscle blood flow; nitric oxide; nitric oxide synthase