L-arginine infusion decreases plasma total homocysteine concentrations through increased nitric oxide production and decreased oxidative status in Type II diabetic patients

Aims/hypothesis. Hyperhomocysteinaemia increases cardiovascular risk in Type H (non-insulin-dependent) diabetes mellitus by augmenting oxidative stress and reducing nitric oxide availability. In vitro, nitric oxide decreases homocysteine by its conversion to the vasodilative and antioxidant compound s-nitrosohomocysteine. We investigated whether or not changes in nitric oxide availability decrease homocysteine concentrations in vivo. Methods. The study group consisted of 20 normotensive, normolipidaemic, non-atherosclerotic Type II diabetic patients in good metabolic control (16 men, 51.2+/-1.4 years) and 15 healthy subjects (12 men, 48.1+/-1.5 years). Circulating concentrations of homocysteine, nitrite+nitrate and sulphydryl groups, a marker of oxidative stress, were assessed at baseline and then 5', 10', 30' and 60' after the intravenous infusion of either L-arginine (3 g in 10 ml saline), the nitric oxide precursor, or vehicle according to a double-blind cross-over randomized protocol. Results. At baseline diabetic patients showed lower plasma sulphydryl group concentrations (491.8+/-16.9 vs 551.3+/-21.0 pmol/l, p<0.04) and nitrite+nitrate (21.4+/-0.8 vs 29.5+/-0.9 mumol/l, p<0.0001) and higher total homocysteine concentrations (11.1+/-0.5 vs 8.3+/-0.6 pmol/l, p<0.002) than the control subjects. After L-arginine infusion, blood pressure levels and total homocysteine concentrations (pless than or equal to0.05) decreased (peak at 5' and 30', respectively) whereas nitric oxide and sulphydryl group concentrations (pless than or equal to0.003) increased (peak at 10' and 30', respectively) in the patients and control subjects. Conclusion/interpretation. Acute L-arginine in fusion in both Type II diabetic patients and healthy subjects decreases plasma total homocysteine concentrations, counteract oxidative stress and increases the availability of nitric oxide.