ACE‐inhibition modulates some endothelial functions in healthy subjects and in normotensive type 1 diabetic patients

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. 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; 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. CONCLUSION: 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.