title: Impaired contraction and endothelium-dependent relaxation in isolated resistance vessels from patients with insulin-dependent diabetes mellitus.
abstract: 1. An increase in capillary blood flow and pressure has been implicated in the pathogenesis of diabetic microangiopathy. Abnormal vascular reactivity of the resistance vasculature may play a contributory role by permitting alterations in regional haemodynamics. 2. We have studied the contractile behavior of isolated resistance arteries from normotensive patients with insulin-dependent diabetes mellitus and non-diabetic matched control subjects. Contractile responses to potassium (123 mmol/l), noradrenaline (10(-8) to 3 x 10(-5) mol/l) and angiotensin II (10(-11) to 3 x 10(-8) mol/l) were recorded. Relaxation studies were performed in maximally contracted vessels using acetylcholine (10(-8) to 10(-5) mol/l) and bradykinin (10(-9) to 10(-6) mol/l) (endothelium-dependent) and sodium nitroprusside (10(-9) to 10(-5) mol/l) (endothelium-independent). 3. The maximal contractile responses to potassium (P < 0.05), noradrenaline (P < 0.01) and angiotensin II (P < 0.01) were depressed in diabetic patients. Relaxation to acetylcholine was impaired (P < 0.05), but was normal with bradykinin and sodium nitroprusside. 4. These results suggest that there may be a defect in the endothelial cell acetylcholine receptor excitation-coupling in diabetes mellitus rather than a decreased ability to synthesize and release endothelium-derived relaxing factor. Impaired contraction and endothelium-dependent relaxation of resistance arteries in diabetic patients may contribute to the development of diabetic microangiopathy by causing an increase in tissue blood flow, a rise in capillary pressure and, as a result, an increase in vascular permeability.
authors.affiliation: Department of Diabetes, Leicester Royal Infirmary, U.K.
authors.forename: P G
authors.initials: PG
authors.lastname: McNally
authors.forename: P A
authors.initials: PA
authors.lastname: Watt
authors.forename: T
authors.initials: T
authors.lastname: Rimmer
authors.forename: A C
authors.initials: AC
authors.lastname: Burden
authors.forename: J R
authors.initials: JR
authors.lastname: Hearnshaw
authors.forename: H
authors.initials: H
authors.lastname: Thurston
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D000804:Angiotensin II / Q000494:pharmacology; D001158:Arteries; D001920:Bradykinin / Q000494:pharmacology; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology*; D003925:Diabetic Angiopathies / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000503:physiopathology*; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D014655:Vascular Resistance; D014661:Vasoconstriction
chemical_list: D000804:Angiotensin II; D009599:Nitroprusside; D000109:Acetylcholine; D011188:Potassium; D001920:Bradykinin; D009638:Norepinephrine