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.
Cassone Faldetta
M
M
Department of Internal Medicine and Public Health, University of L'Aquila, Italy.
Laurenti
O
O
Desideri
G
G
Bravi
M C
MC
De Luca
O
O
Marinucci
M C
MC
De Mattia
G
G
Ferri
C
C
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