L-arginine-nitric oxide kinetics in normal and type 2 diabetic subjects: a stable-labelled [sup.15]N arginine approach. (Pathophysiology)

Defective endothelium is a key event in the development of atherosclerosis in diabetes: alteration of the L-arginine-nitric oxide (NO) pathway has been suggested. We propose a modeling approach of the L-arginine-NO pathway in vivo in both control and type 2 diabetic subjects based on the intravenous bolus injection of L-[[sup.15]N]arginine and subsequent noncompartmental and compartmental model analysis of L-[[sup.15]N] arginine in plasma and [[sup.15]N]nitrate in the urine. No differences in arginine kinetics were observed between normal subjects and diabetic patients. [[sup.15]N]nitrates were detectable up to 48 h from the L-[sup.15]ℕarginine administration; no differences were found in the tracer-to-tracee ratio in each urine collection. However, the NO synthesis in plasma from arginine was lower (P = 0.05 for the noncompartmental and 0.1208 for the compartmental analysis, by Mann-Whitney test) in diabetic patients than in control subjects when expressed both in absolute terms (50% decrease) and as percentage of NO turnover (30% decrease). This new modeling approach of L-arginine-NO pathway provides a detailed picture of arginine kinetics and nitrate metabolism. From our data, it appears that noncomplicated type 2 diabetic patients have a decreased conversion of arginine to NO.
Endothelial dysfunction is a possible culprit of the accelerated atherosclerosis in diabetic patients. Several different mechanisms negatively act on endothelial function (1). The assessment of endothelial function in humans can [...]