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Oral L-arginine inhibits platelet aggregation but does not enhance endothelium-dependent dilation in healthy young men.
J Am Coll Cardiol 1995; 26(4):1054-61JACC

Abstract

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 +/- 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.

Authors+Show Affiliations

Department of Cardiology, Royal Prince Alfred Hospital, Sydney, Australia.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Comparative Study
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

7560599

Citation

Adams, M R., et al. "Oral L-arginine Inhibits Platelet Aggregation but Does Not Enhance Endothelium-dependent Dilation in Healthy Young Men." Journal of the American College of Cardiology, vol. 26, no. 4, 1995, pp. 1054-61.
Adams MR, Forsyth CJ, Jessup W, et al. Oral L-arginine inhibits platelet aggregation but does not enhance endothelium-dependent dilation in healthy young men. J Am Coll Cardiol. 1995;26(4):1054-61.
Adams, M. R., Forsyth, C. J., Jessup, W., Robinson, J., & Celermajer, D. S. (1995). Oral L-arginine inhibits platelet aggregation but does not enhance endothelium-dependent dilation in healthy young men. Journal of the American College of Cardiology, 26(4), pp. 1054-61.
Adams MR, et al. Oral L-arginine Inhibits Platelet Aggregation but Does Not Enhance Endothelium-dependent Dilation in Healthy Young Men. J Am Coll Cardiol. 1995;26(4):1054-61. PubMed PMID: 7560599.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Oral L-arginine inhibits platelet aggregation but does not enhance endothelium-dependent dilation in healthy young men. AU - Adams,M R, AU - Forsyth,C J, AU - Jessup,W, AU - Robinson,J, AU - Celermajer,D S, PY - 1995/10/1/pubmed PY - 1995/10/1/medline PY - 1995/10/1/entrez SP - 1054 EP - 61 JF - Journal of the American College of Cardiology JO - J. Am. Coll. Cardiol. VL - 26 IS - 4 N2 - 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 +/- 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. SN - 0735-1097 UR - https://www.unboundmedicine.com/medline/citation/7560599/Oral_L_arginine_inhibits_platelet_aggregation_but_does_not_enhance_endothelium_dependent_dilation_in_healthy_young_men_ L2 - https://linkinghub.elsevier.com/retrieve/pii/0735-1097(95)00257-9 DB - PRIME DP - Unbound Medicine ER -