Improvement in endothelial function by angiotensin converting enzyme inhibition in insulin-dependent diabetes mellitus.
We postulated that nitric oxide (NO)-mediated endothelial function would be improved by acute and short-term treatment with an angiotensin converting enzyme (ACE) inhibitor in patients with type I diabetes mellitus, in whom endothelial function is depressed. Nine type I diabetic patients and eight healthy subjects underwent forearm blood flow measurement using strain gauge plethysmography during intraarterial infusion of incremental doses of endothelium-dependent (acetylcholine [ACh]) and endothelium-independent (sodium nitroprusside [SNP]) vasodilators. Pretreatment ACh responses were depressed in diabetic patients relative to the normal subjects (P < 0.05). No difference between the groups was evident in response to SNP. Acute ACE inhibition (with intrabrachial enalaprilat) enhanced ACh responses in the diabetic patients (P < 0.005), with a further improvement evident after 1 mo of oral therapy with enalapril (P < 0.001) when ACh responses were normalized. ACE inhibition did not affect SNP responses. We conclude that acute administration of the ACE inhibitor, enalaprilat, enhances NO-mediated endothelial function in type I diabetic patients, with further improvement evident after 4 wk of enalapril therapy.
O'Driscoll
G
G
Department of Cardiology and Medicine, Royal Perth Hospital, Australia. gerrodri@dunamis.rph.uwa.edu.au
Green
D
D
Rankin
J
J
Stanton
K
K
Taylor
R
R
D000284:Administration, Oral; D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000503:physiopathology*; D004656:Enalapril / Q000008:administration & dosage*; D015773:Enalaprilat / Q000008:administration & dosage*; D004727:Endothelium / Q000187:drug effects / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000502:physiology
D000806:Angiotensin-Converting Enzyme Inhibitors; D009569:Nitric Oxide; D004656:Enalapril; D015773:Enalaprilat