Oral L-arginine inhibits platelet aggregation but does not enhance endothelium-dependent dilation in healthy young men.
OBJECTIVE
Our aim was to assess the effect of oral L-arginine on endothelial or platelet physiology in humans.


BACKGROUND
L-Arginine is the substrate for nitric oxide synthesis, and in cholesterol-fed rabbits, oral L-arginine improves endothelium-dependent dilation, inhibits platelet aggregation and reduces atheroma. In hypercholesterolemic humans, intravenous L-arginine immediately improves endothelium-dependent dilation; however, the vascular effects of oral L-arginine in healthy humans have not previously been investigated.


METHODS
In a prospective, double-blind, randomized crossover trial, 12 healthy young men 27 to 37 years old took L-arginine (7 g three times daily) or placebo for 3 days each, separated by a washout period of 7 to 14 days.


RESULTS
After L-arginine, plasma levels of arginine (mean +/- SEM 303 +/- 36 vs. 128 +/- 12 mumol/liter, p = 0.01) and urea (6.7 +/- 0.5 vs. 5.2 +/- 0.2 mmol/liter, p < 0.01) were higher than levels measured after placebo, and platelet aggregation in response to adenosine diphosphate was markedly impaired (37 +/- 12% vs. 81 +/- 3%, p = 0.02). The inhibition of platelet aggregation correlated with the plasma level of L-arginine (r = 0.74, p = 0.01), and it could be completely or partially reversed by ex vivo incubation with N-monomethyl-L-arginine, a specific nitric oxide synthase inhibitor. Platelet cyclic guanosine monophosphate levels were higher after oral L-arginine than at baseline (1.91 +/- 0.46 vs. 1.38 +/- 0.40 pmol/10(9) platelets, p = 0.04). No changes were seen in fasting lipid levels, heart rate, blood pressure, endothelium-dependent dilation of the brachial artery (measured in response to reactive hyperemia, using external vascular ultrasound) (6.1 +/- 0.7% vs. 6.5 +/- 0.7%, p = NS) or in plasma levels of nitrosylated proteins (a marker of in vivo nitric oxide production) (3.5 +/- 0.5 vs. 3.3 +/- 0.4 mumol/liter, p = NS) 1 to 1.5 h after the last dose of L-arginine.


CONCLUSIONS
In these healthy young adult men, oral L-arginine inhibited platelet aggregation by way of the nitric oxide pathway. However, it had no effect on systemic hemodynamic variables, plasma nitrosylated protein levels or endothelium-dependent dilation. Therefore, at certain doses, oral L-arginine may result in a relatively platelet-specific increase in nitric oxide production.
Adams
M R
MR
Department of Cardiology, Royal Prince Alfred Hospital, Sydney, Australia.
Forsyth
C J
CJ
Jessup
W
W
Robinson
J
J
Celermajer
D S
DS
D000284:Administration, Oral; D000328:Adult; D001120:Arginine / Q000097:blood / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D018592:Cross-Over Studies; D006152:Cyclic GMP / Q000097:blood; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011446:Prospective Studies; D014664:Vasodilation / Q000187:drug effects*
D010975:Platelet Aggregation Inhibitors; D009569:Nitric Oxide; D001120:Arginine; D006152:Cyclic GMP