Author + information
- Received February 2, 1995
- Revision received May 3, 1995
- Accepted May 5, 1995
- Published online October 1, 1995.
- Mark R. Adams, MBBS*,
- Cecily J. Forsyth, MBBS, FRACP*,
- Wendy Jessup, PhD†,
- Jacqui Robinson, RN* and
- David S. Celermajer, PhD, FRACP*,†,*
- ↵*Address for correspondence: Dr. David S. Celermajer, Department of Cardiology, Royal Prince Alfred Hospital. Missenden Road, Camperdown, 2050, Sydney, New South Wales, Australia.
Objectives. 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 ± 12μmol/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/109platelets, p = 0.04). No changes were seen in fasting lipid levels, heart rate, blood pressure, endotheliumdependent 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 μmol/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.
This work was supported in part by grants from the National Health and Medical Research Council of Australia, National Heart Foundation of Australia and Royal Australasian College of Physicians, Sydney. Dr. Adams is supported by the University of Sydney and Dr. Celermajer by the National Health and Medical Research Council of Australia.
- Received February 2, 1995.
- Revision received May 3, 1995.
- Accepted May 5, 1995.
- American College of Cardiology