title: Heightened norepinephrine-mediated vasoconstriction in type 2 diabetes.
abstract: Adrenergic responsiveness (AR) appears to be increased in subjects with diabetes, but measurement of arterial AR in normotensive people with type 2 diabetes mellitus has not been previously reported. We sought to determine whether, compared with control subjects, there is increased arterial AR in type 2 diabetes mellitus and its relationship to the level of systemic sympathetic nervous system activity (SNSa). We studied 15 type 2 diabetic subjects aged 57 +/- 3 years without hypertension or clinical signs of autonomic neuropathy and 13 age-matched control subjects aged 55 +/- 2 years. We assessed vascular alpha-AR by measuring forearm blood flow (FABF) by venous occlusion plethysmography during intrabrachial artery norepinephrine (NE) and phentolamine infusions, as well as arterial plasma NE levels and the extravascular NE release rate (NE2) derived from 3H-NE kinetics, as estimates of systemic SNSa. The vasoconstricting effect of NE during intrabrachial artery NE infusion was greater in type 2 diabetes compared with control subjects (P = .02). The vasodilating effect of phentolamine was greater in type 2 diabetics compared with control subjects (P = .05), suggesting increased endogenous arterial alpha-adrenergic tone. Arterial plasma NE levels (control v type 2, 1.8 +/- 0.10 v 1.84 +/- 0.14 nmol/L, P = .86) and NE2 (control vtype 2, 11.8 +/- 1.54 v 13.3 +/- 0.89 nmol/min/m2, P = .39) were similar in the two groups. In summary, in type 2 diabetes compared with control subjects, (1) the vasoconstriction response to intraarterial NE is greater, (2) plasma NE and NE2 are similar, suggesting similar levels of systemic SNSa, and (3) arterial alpha-adrenergic tone is greater. We conclude that subjects with type 2 diabetes demonstrate inappropriately increased alpha-AR for their level of systemic SNSa.
authors.affiliation: Department of Internal Medicine, and Institute of Gerontology, University of Michigan, Ann Arbor, USA.
authors.forename: R V
authors.initials: RV
authors.lastname: Hogikyan
authors.forename: A T
authors.initials: AT
authors.lastname: Galecki
authors.forename: J B
authors.initials: JB
authors.lastname: Halter
authors.forename: M A
authors.initials: MA
authors.lastname: Supiano
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D004837:Epinephrine / Q000097:blood; D005260:Female; D005542:Forearm / Q000098:blood supply; D005951:Glucose Tolerance Test; D006801:Humans; D007269:Injections, Intra-Arterial; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood / Q000494:pharmacology / Q000502:physiology*; D010646:Phentolamine / Q000494:pharmacology; D012016:Reference Values; D012039:Regional Blood Flow / Q000187:drug effects; D014661:Vasoconstriction / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D000317:Adrenergic alpha-Antagonists; D014662:Vasoconstrictor Agents; D009638:Norepinephrine; D004837:Epinephrine; D010646:Phentolamine