title: Smoking attenuates the vasoconstrictor response to noradrenaline in type I diabetic patients and normal subjects: possible relevance to diabetic nephropathy.
abstract: Exaggerated vascular reactivity has been implicated in the pathogenesis of diabetic nephropathy, and several studies suggest that smoking accelerates its progression. We therefore assessed the vasoactive effects of smoking by comparing noradrenaline-induced vasoconstriction in dorsal hand-veins between smoking and non-smoking groups of Type I diabetic patients with and without microalbuminuria and in non-diabetic subjects. Smokers had a significantly higher dose causing 50% vasoconstriction (reduced sensitivity to noradrenaline) in all three groups: microalbuminuric diabetic smokers vs. nonsmokers, 20.2(4.6) (SEM) vs. 6.6(2.3) ng min-1 (P = 0.02); normoalbuminuric, 76.9(29.4) vs. 22.8(9.1) ng min-1 (P = 0.03); non-diabetic subjects, 97.8(30.0) vs. 38.0(12.8) ng min-1 (P = 0.01). Both microalbuminuric diabetic groups showed significantly greater sensitivity to noradrenaline-induced vasoconstriction than the other smoking and non-smoking groups, respectively (P < 0.01). Vasoconstrictors responses to noradrenaline are attenuated in smokers, possibly due to alpha-adrenoceptor down-regulation. Smoking could increase urinary albumin losses and accelerate renal damage through catecholamine surges which raise systemic and, perhaps, intraglomerular blood pressure. This hypothesis deserves further consideration.
authors.affiliation: Department of Medicine, University of Liverpool, UK.
authors.forename: C W
authors.initials: CW
authors.lastname: Bodmer
authors.forename: D T
authors.initials: DT
authors.lastname: Valentine
authors.forename: E A
authors.initials: EA
authors.lastname: Masson
authors.forename: M W
authors.initials: MW
authors.lastname: Savage
authors.forename: D
authors.initials: D
authors.lastname: Lake
authors.forename: G
authors.initials: G
authors.lastname: Williams
mesh_terms: D000328:Adult; D000419:Albuminuria / Q000209:etiology; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000209:etiology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000494:pharmacology*; D012907:Smoking / Q000009:adverse effects / Q000503:physiopathology*; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D009638:Norepinephrine