Improvement in endothelial function by angiotensin-converting enzyme inhibition in non-insulin-dependent diabetes mellitus

J Am Coll Cardiol. 1999 May;33(6):1506-11. doi: 10.1016/s0735-1097(99)00065-0.


Objectives: The aim of this study was to assess the effect of angiotensin-converting enzyme (ACE) inhibition with enalapril on forearm endothelial function in subjects with type II diabetes mellitus.

Background: Endothelial function is depressed in the presence of conventional risk factors for atherosclerosis, and various therapies, such as lipid-lowering therapy in hypercholesterolemia, can improve endothelial-mediated vasodilation. ACE inhibition has improved such function in several conditions including type I diabetes, but there is no evidence for a beneficial effect in type II diabetes.

Methods: The influence of enalapril (10 mg twice daily for 4 weeks) on endothelium-dependent and -independent vasodilator function was determined in 10 type II diabetic subjects using a double-blinded placebo-controlled crossover protocol. Forearm blood flow was measured using strain-gage plethysmography and graded intrabrachial infusion of acetylcholine (ACh), N(G)-monomethyl-L-arginine (LNMMA) and sodium nitroprusside (SNP).

Results: Enalapril increased the response to the endothelium-dependent vasodilator, ACh (p < 0.02) and the vasoconstrictor response to the nitric oxide (NO) synthase inhibitor, LNMMA (p < 0.002). No difference was evident in the response to SNP.

Conclusions: In type II diabetic subjects without evidence of vascular disease, the ACE inhibitor enalapril improved stimulated and basal NO-dependent endothelial function. The study extends the spectrum of beneficial effects demonstrated to result from ACE inhibition in diabetes.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine
  • Aged
  • Angiotensin-Converting Enzyme Inhibitors / administration & dosage*
  • Angiotensin-Converting Enzyme Inhibitors / adverse effects
  • Blood Flow Velocity / drug effects
  • Blood Flow Velocity / physiology
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Diabetic Angiopathies / drug therapy
  • Diabetic Angiopathies / physiopathology
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Schedule
  • Enalapril / administration & dosage*
  • Enalapril / adverse effects
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / physiopathology
  • Forearm / blood supply
  • Humans
  • Middle Aged
  • Nitroprusside
  • omega-N-Methylarginine


  • Angiotensin-Converting Enzyme Inhibitors
  • Nitroprusside
  • omega-N-Methylarginine
  • Enalapril
  • Acetylcholine