L-arginine infusion decreases plasma total homocysteine concentrations through increased nitric oxide production and decreased oxidative status in Type II diabetic patients.
OBJECTIVE
Hyperhomocysteinaemia increases cardiovascular risk in Type II (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 micro mol/l, p<0.04) and nitrite+nitrate (21.4+/-0.8 vs 29.5+/-0.9 micro mol/l, p<0.0001) and higher total homocysteine concentrations (11.1+/-0.5 vs 8.3+/-0.6 micro mol/l, p<0.002) than the control subjects. After L-arginine infusion, blood pressure levels and total homocysteine concentrations ( p< or =0.05) decreased (peak at 5' and 30', respectively) whereas nitric oxide and sulphydryl group concentrations ( p< or =0.003) increased (peak at 10' and 30', respectively) in the patients and control subjects.


CONCLUSIONS
Acute L-arginine infusion in both Type II diabetic patients and healthy subjects decreases plasma total homocysteine concentrations, counteract oxidative stress and increases the availability of nitric oxide.
Department of Internal Medicine and Public Health, University of L'Aquila, Italy.
M
M
Cassone Faldetta
O
O
Laurenti
G
G
Desideri
M C
MC
Bravi
O
O
De Luca
M C
MC
Marinucci
G
G
De Mattia
C
C
Ferri
D001120:Arginine / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D004311:Double-Blind Method; D005260:Female; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000096:biosynthesis*; D009573:Nitrites / Q000097:blood; D009994:Osmolar Concentration; D018384:Oxidative Stress; D012016:Reference Values; D013438:Sulfhydryl Compounds / Q000097:blood
D009566:Nitrates; D009573:Nitrites; D013438:Sulfhydryl Compounds; D006710:Homocysteine; D009569:Nitric Oxide; D001120:Arginine