title: ACE-inhibition modulates some endothelial functions in healthy subjects and in normotensive type 1 diabetic patients.
abstract: BACKGROUND
  The usefulness of treatment with an angiotensin-converting enzyme-inhibitor (ACE-inhibitor) in normotensive patients with type 1 diabetes is controversial. We investigated whether ACE-inhibition improves endothelial function in such patients and compared the responses to those in healthy subjects.
  
  
  METHODS
  We studied 23 healthy volunteers (controls, aged 29.8 [SD 7.0] years) and 24 type 1 diabetic patients (aged 28.7 [9. 6] years; HbA1c 8.1 [1.2]%; diabetes duration 13.8 [2-30] years; blood pressure < 140/90 mm Hg; 7 with microalbuminuria) after 5 weeks of ACE-inhibition (quinapril, 10 mg day-1) and placebo in a randomized, double-blind cross-over design. Estimates of endothelial function obtained were by flow-mediated vasodilation and plasma levels of endothelium-derived proteins.
  
  
  RESULTS
  As estimated from the measurements on placebo, type 1 diabetic patients, as compared to the controls, had some impairment of endothelial function: plasma tissue-type plasminogen activator levels were lower (3.5 vs. 5.4 ng mL(-1), P<0.05), but there were no significant differences in brachial artery flow-mediated vasodilation or plasma levels of von Willebrand Factor, endothelin-1, plasminogen activator inhibitor-1, soluble E-selectin or vascular cell adhesion molecule-1. As compared to placebo, ACE-inhibition increased flow-mediated vasodilation in controls (by 3.84% points [95% CI, 0.66 - 7.02], P<0.05), but not in type 1 diabetic patients (0.82% points [95% CI, -2.72 - 4.36], P = 0.64; P = 0.08 vs. controls). On ACE-inhibition soluble E-selectin levels decreased both in controls (from 43.0 to 37.0 ng mL(-1), P<0.01) and in type 1 diabetic patients (from 41.0 to 39.0 ng mL(-1), P = 0.09). Other endothelial markers did not change during ACE-inhibition.
  
  
  CONCLUSIONS
  Normotensive type 1 diabetic patients with normoalbuminara or microalbuminuria have mild endothelial dysfunction. Short-term ACE-inhibition improves endothelial function as reflected by a decreased sE-selectin in healthy subjects and in normotensive type 1 diabetic patients. In healthy subjects, ACE-inhibition increases flow-mediated vasodilation. In contrast, in type 1 diabetic patients, ACE-inhibition does not affect flow-mediated vasodilation.
authors.affiliation: Department of Clinical Chemistry, Academisch Ziekenhuis Vrije Universiteit, and Institute for Cardiovascular Research (ICaR), Vrije Universiteit, Amsterdam, The Netherlands. C.Schalkwijk@azvu.nl
authors.forename: C G
authors.initials: CG
authors.lastname: Schalkwijk
authors.forename: R A
authors.initials: RA
authors.lastname: Smulders
authors.forename: J
authors.initials: J
authors.lastname: Lambert
authors.forename: A J
authors.initials: AJ
authors.lastname: Donker
authors.forename: C D
authors.initials: CD
authors.lastname: Stehouwer
mesh_terms: D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D015415:Biomarkers; D001916:Brachial Artery / Q000502:physiology; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000150:complications*; D003925:Diabetic Angiopathies / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D019040:E-Selectin / Q000097:blood; D016232:Endothelins / Q000097:blood; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006801:Humans; D007546:Isoquinolines / Q000008:administration & dosage*; D008297:Male; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D000077583:Quinapril; D044005:Tetrahydroisoquinolines; D010959:Tissue Plasminogen Activator / Q000097:blood; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood; D014664:Vasodilation / Q000187:drug effects; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D015415:Biomarkers; D019040:E-Selectin; D016232:Endothelins; D007546:Isoquinolines; D017395:Plasminogen Activator Inhibitor 1; D044005:Tetrahydroisoquinolines; D019010:Vascular Cell Adhesion Molecule-1; D014841:von Willebrand Factor; D010959:Tissue Plasminogen Activator; D000077583:Quinapril