Arginase Inhibition and Microvascular Endothelial Function in Type 2 Diabetes

Background

The development of microvascular complications in diabetes is a complex process, in which endothelial dysfunction is of importance. Emerging evidence suggests that arginase is a key mediator of endothelial dysfunction in type 2 diabetes mellitus (T2DM) by reciprocally regulating nitric oxide bioavailability. The aim of this study was to test the hypothesis that arginase activity is increased and that arginase contributes to microvascular endothelial function in patients with T2DM and microvascular dysfunction.

Method

Microvascular endothelium-dependent and -independent vasodilatation are investigated in patients with T2DM (n =12) and healthy age-matched control subjects (n =12) with laser-Doppler flowmetry during iontophoretic application of acetylcholine and sodium nitroprusside, respectively, before and after intra-arterial administration of the arginase inhibitor N-hydroxy-nor-L-arginine (0.1 mg/min) for 120 min.

Inclusion criteria

• Clinical diagnosis of type 2 diabetes mellitus and microvascular dysfunction defined as microalbuminuria > 3.0 mg/mmol or presence of retinopathy.

Exclusion criteria

• Myocardial infarction or unstable angina within the last three months,
• Changed dose of any vasodilator drug during the preceding six weeks,
• Ongoing treatment with warfarin
• Concomitant disease that may have interfered with the possibility for the patients to comply with or complete the study protocol