title: Glucose-stimulated insulin secretion causes an insulin-dependent nitric oxide-mediated vasodilation in the blood supply of the rat sciatic nerve.
abstract: This study tested the hypothesis that acute hyperglycemia reduces sciatic nerve blood flow in Sprague-Dawley rats. Anesthetized rats underwent cannulation of their right jugular vein (for anesthetic/nutrient/drug infusion) and right carotid artery (for continuous blood pressure measurement via pressure transducer). The left sciatic nerve was exposed and nerve blood velocity (NBV) was assessed from an arterial segment lying superficially along the sciatic nerve (Doppler ultrasound, 40 MHz). NBV and mean arterial pressure (MAP) values were collected, and an index of nerve vascular conductance (NVC) was established (NBV/MAP) at baseline and at 5, 10, 20, and 30 min (and 80 min for insulin) following 1) low glucose infusion, 1 g/kg (50% solution); 2) high glucose infusion, 3 g/kg; 3) high glucose infusion in the absence of a functioning pancreas; 4) euglycemic hyperinsulinemic clamp-insulin infusion (10 mU·kg⁻¹·min⁻¹; 0.4 IU/ml); 5) high glucose infusion + NG-nitro-L-arginine methyl ester (L-NAME) infusion (30 mg/kg); and 6) L-NAME alone followed 20 min later by high glucose infusion. High glucose infusion increased NVC by ~120% relative to baseline (P < 0.001), and this dilation was attenuated in rats without a functioning pancreas (i.e., without insulin secretion) (P = 0.004) and following L-NAME infusion (P = 0.011). Therefore, the vasodilation in rat sciatic nerve during glucose infusion was dependent upon the insulin response and acted through a nitric oxide synthase pathway.
authors.affiliation: Neurovascular Research Laboratory, School of Kinesiology, Western University, London, Ontario, Canada.
authors.forename: T Dylan
authors.initials: TD
authors.lastname: Olver
authors.forename: Louis
authors.initials: L
authors.lastname: Mattar
authors.forename: Kenneth N
authors.initials: KN
authors.lastname: Grisé
authors.forename: Jasna
authors.initials: J
authors.lastname: Twynstra
authors.forename: Earl G
authors.initials: EG
authors.lastname: Noble
authors.forename: James C
authors.initials: JC
authors.lastname: Lacefield
authors.forename: J Kevin
authors.initials: JK
authors.lastname: Shoemaker
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology*; D015309:Glucose Clamp Technique; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
chemical_list: D001786:Blood Glucose; D004791:Enzyme Inhibitors; D007328:Insulin; D009569:Nitric Oxide; D005947:Glucose; D019331:NG-Nitroarginine Methyl Ester
keywords: Doppler ultrasound; glucose; insulin; nerve blood flow; nitric oxide