ACE inhibitors improve endothelial function in type 1 diabetic patients with normal arterial pressure and microalbuminuria.

OBJECTIVE: The purpose of this study was to test whether a short-course treatment with ACE inhibitors may restore endothelium-dependent and/or -independent vasodilation in the femoral artery of microalbuminuric patients with type 1 diabetes and normal arterial pressure. RESEARCH DESIGN AND METHODS: We studied nine normotensive microalbuminuric type 1 diabetic patients and two groups of control subjects matched for femoral artery diameter to type 1 diabetic patients after placebo (control group A, n = 17) and ACE inhibitor (control group B, n = 18) treatment, respectively. The patients were enrolled in a double-blind cross-over study with a 1-week trial of either placebo, captopril (25 mg t.i.d.), or enalapril (10 mg/day) in randomized order to ascertain whether short-term ACE inhibition obtained with (captopril) or without (enalapril) a sulfhydryl donor molecule ameliorates vessel wall function. Endothelium-mediated flow-dependent vasodilation and endothelium-independent vasodilation were evaluated in the right common femoral artery by echo Doppler. RESULTS: Both captopril and enalapril normalized (control group B 22.9+/-3.2% per 8 min) endothelium-dependent response (19.6+/-7.5 and 18.0+/-5.3 vs. -10.4+/-4.1% per 8 min, P < 0.01, for both captopril and enalapril versus placebo, respectively) in the type 1 diabetic patients. Captopril (28.4+/-3.5 vs. 17.1+/-3.5% per 5 min during placebo, P < 0.05) but not enalapril (20.1+/-3.0 vs. 31.7+/-2.8% per 5 min, P < 0.05 for enalapril versus control group B, and NS for captopril vs. control group B) ameliorated endothelium-independent vasodilation in type 1 diabetic patients. CONCLUSIONS: ACE inhibition improves endothelium-dependent vasodilation in the femoral artery of normotensive microalbuminuric type 1 diabetic patients. Captopril also ameliorates endothelium-independent vasodilation, possibly through its sulfhydryl donor properties. These results may be of pathophysiological relevance to prevent cardiovascular complications in these patients.

Noninvasive detection of functional alterations of the arterial wall in IDDM patients with and without microalbuminuria.

OBJECTIVE: To test endothelial function in a group of 10 normoalbuminuric and eight microalbuminuric insulin-dependent diabetes mellitus patients (ages 28 +/- 3 [mean +/- SE] and 28 +/- 1 years, respectively), in comparison with 16 control subjects (age 35 +/- 2 years, normal subjects vs. diabetic subjects P = NS), to identify prestructural abnormalities of the arterial wall. An early stage of vascular involvement seems in fact to be characterized by functional alterations of endothelial control on vascular tone and wall interaction with circulating cells. Furthermore, many recent studies suggest the importance of microalbuminuria as an early marker not only of nephropathy but also of retinopathy and macroangiopathy. RESEARCH DESIGN AND METHODS: Endothelium-mediated flow-dependent vasodilation and endothelium-independent vasodilation (induced by glyceryl trinitrate administration) were evaluated in the right common femoral artery by echo-Doppler ultrasound. Arterial wall distensibility was evaluated at the common femoral artery by an echo-tracking system. RESULTS: In spite of a comparable increase in flow velocity, endothelium-mediated vasodilation was significantly reduced in diabetic subjects, particularly in microalbuminuric patients. Endothelium-independent vasodilation was also significantly impaired in diabetic subjects, particularly in microalbuminuric subjects; whereas arterial wall distensibility, an index of the viscoelastic properties of the wall, was similar in the three groups. CONCLUSIONS: These results confirm a reduced vasodilatory capacity in diabetes mellitus, with a more marked alteration in microalbuminuric diabetic subjects. This reliable, noninvasive evaluation of arterial function is particularly useful for early diagnosis of vascular involvement.

Non-invasive detection of early endothelial dysfunction in hypercholesterolaemic subjects.

Hypercholesterolaemia is associated with accelerated atherogenesis. Before the evidence of morphological lesions or plaques, endothelial dysfunctions, such as impairment in endothelium-dependent vascular tone regulation, may occur. We studied 32 subjects, 16 with primary hypercholesterolaemia and 16 normocholesterolaemic controls. Flow-dependent vasodilation, an endothelium-dependent phenomenon, was evaluated by measuring femoral artery diameter and flow velocity in basal conditions and during distal post-ischemic hyperaemia, using a high resolution echo-Doppler. Arterial distensibility and compliance were evaluated for the common carotid and femoral arteries, using a pulsed echo-tracking system and measuring the absolute and relative stroke change in arterial diameter. In the hypercholesterolaemic group there was no flow-dependent arterial relaxation, indicated by the area under the curve of percentage diameter variation as a function of time. This parameter was inversely correlated with both total and LDL-cholesterol values in all population subjects. No difference was observed between the two groups in endothelium-independent vasodilation induced by glyceryl trinitrate administration or arterial wall distensibility and compliance, confirming the hypothesis of a functional defect.