ACE-inhibition modulates some endothelial functions in healthy subjects and in normotensive type I diabetic patients

Citation
Cg. Schalkwijk et al., ACE-inhibition modulates some endothelial functions in healthy subjects and in normotensive type I diabetic patients, EUR J CL IN, 30(10), 2000, pp. 853-860
Citations number
42
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Medical Research General Topics
Journal title
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
ISSN journal
00142972 → ACNP
Volume
30
Issue
10
Year of publication
2000
Pages
853 - 860
Database
ISI
SICI code
0014-2972(200010)30:10<853:AMSEFI>2.0.ZU;2-J
Abstract
Background The usefulness of treatment with an angiotensin-converting enzym e-inhibitor (ACE-inhibitor) in normotensive patients with type 1 diabetes i s controversial. We investigated whether ACE-inhibition improves endothelia l function in such patients and compared the responses to those in healthy subjects. Design 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; HbA(1c) 8.1 [1.2] %; diabetes duration 13.8 [2-30] years; blood pressure < 140/90 mmHg; 7 wit h 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 pla sma levels of endothelium-derived proteins. Results As estimated from the measurements on placebo, type 1 diabetic pati ents, as compared to the controls, had some impairment of endothelial funct ion: 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 brachi al artery flow-mediated vasodilation or plasma levels of von Willebrand Fac tor, endothelin-l, 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 nor 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-inhibi tion. Conclusion Normotensive type 1 diabetic patients with normoalbuminara or mi croalbuminuria have mild endothelial dysfunction. Short-term ACE-inhibition improves endothelial function as reflected by a decreased sE-selectin in h ealthy subjects and in normotensive type I diabetic patients. In healthy su bjects, ACE-inhibition increases flow-mediated vasodilation. In contrast, i n type I diabetic patients, ACE-inhibition does not affect flow-mediated va sodilation.