title: Elevated skeletal muscle blood flow in noncomplicated type 1 diabetes mellitus: role of nitric oxide and sympathetic tone.
abstract: Capillary hyperperfusion precedes and contributes to the occurrence of diabetic microangiopathy. Vascular tone is regulated by the balance of vasodilating and vasoconstricting factors, of which nitric oxide (NO; an endothelium dependent vasodilator) and norepinephrine (NE; a potent vasoconstrictor), respectively, are of primary importance. To investigate the role of these factors in hyperperfusion, we measured forearm blood flow (FBF) in 50 patients with noncomplicated type 1 diabetes (DP) and 50 healthy control subjects (CS) under baseline conditions and during intrabrachial infusion of N(G)-monomethyl-L-arginine (L-NMMA), an endothelium-dependent vasoconstrictor, and acetylcholine (ACh), an endothelium-dependent vasodilator. Furthermore, we determined arterial plasma NE concentration at baseline and then determined alpha-adrenergic receptor sensitivity by measuring FBF response to intra-arterially infused NE. We found that basal FBF was increased in DP (2.9+/-0.1 versus 2.0+/-0.1 mL. min(-1). dL(-1) in CS; P<0.01). L-NMMA caused a similar vasoconstriction in both groups (28.5+/-1. 7% in DP versus 31.2+/-2.2% in CS; P=NS). Maximum blood flow during infusion of ACh was not different (23.3+/-1.9 mL. min(-1). dL(-1) in DP versus 20.1+/-1.6 in CS). Arterial plasma NE concentrations were significantly decreased in DP (0.57+/-0.03 versus 0.81+/-0.05 nmol/L in CS; P<0.01). The vasoconstrictive effect of NE was increased in DP (slope log dose-response curve, 31.3+/-1.5 versus 24.3+/-1.8 in CS; P<0.01). We conclude that basal FBF is increased in noncomplicated type 1 diabetes. We found no evidence of a disturbance of basal or stimulated NO production. Arterial plasma NE concentrations are decreased in noncomplicated type 1 diabetes. This may explain the vasodilatation at baseline and the increased vascular response to intra-arterially NE.
authors.affiliation: Department of General Internal Medicine, University Hospital Nijmegen St Radboud, Nijmegen, The Netherlands. g.vervoort@aig.azn.nl
authors.forename: G
authors.initials: G
authors.lastname: Vervoort
authors.forename: J F
authors.initials: JF
authors.lastname: Wetzels
authors.forename: J A
authors.initials: JA
authors.lastname: Lutterman
authors.forename: L G
authors.initials: LG
authors.lastname: van Doorn
authors.forename: J H
authors.initials: JH
authors.lastname: Berden
authors.forename: P
authors.initials: P
authors.lastname: Smits
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply*; D009569:Nitric Oxide / Q000502:physiology*; D009638:Norepinephrine / Q000097:blood; D011942:Receptors, Adrenergic, alpha / Q000502:physiology; D012039:Regional Blood Flow / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000502:physiology*; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D011942:Receptors, Adrenergic, alpha; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D000109:Acetylcholine; D009638:Norepinephrine