Chronic dietary supplementation with L-arginine inhibits platelet aggregation and thromboxane A2 synthesis in hypercholesterolaemic rabbits in vivo

Cardiovasc Res. 1998 Mar;37(3):756-64. doi: 10.1016/s0008-6363(97)00295-2.

Abstract

Objectives: L-arginine exerts anti-atherosclerotic effects in hypercholesterolaemic rabbits via modulating endogenous NO production. We investigated whether L-arginine inhibits thromboxane formation in vivo and platelet aggregation ex vivo in this animal model.

Methods: The urinary excretion rates of 2,3-dinor-6-keto-PGF1 alpha (major urinary metabolite of PGI2) and 2,3-dinor-TXB2 (major urinary metabolite of thromboxane A2) were used as indicators of platelet-endothelial cell interactions in vivo. Rabbits were fed 1% cholesterol (Cholesterol group, N = 8), 1% cholesterol plus 2.25% L-arginine (Cholesterol + L-arginine, N = 8), or normal rabbit chow (Control, N = 4) for 12 weeks. Urine samples were collected in weekly intervals. At the end of the study period platelet aggregation ex vivo and endothelium-dependent and -independent vascular function of isolated aortic rings in vitro was assessed.

Results: Urinary 2,3-dinor-TXB2 excretion significantly increased in the cholesterol group (p < 0.05), and endogenous NO formation (measured as urinary nitrate excretion) decreased (p < 0.05). Both parameters were significantly correlated with each other (R = 0.48, p < 0.01). L-arginine partly restored urinary nitrate excretion and significantly reduced TXA2 production to values even below those in the control group (p < 0.001). Urinary 2,3-dinor-6-keto-PGF1 alpha excretion increased in early hypercholesterolaemia and returned to control values in the second half of the study period. The early increase in urinary 2,3-dinor-6-keto-PGF1 alpha excretion was attenuated by L-arginine. Platelet aggregation was significantly enhanced in cholesterol-fed rabbits and attenuated by dietary L-arginine. L-arginine also improved the impaired endothelium-dependent relaxations to ADP, and normalized the vasoconstrictor effects of 5-HT in isolated aortic rings.

Conclusions: Cholesterol-feeding enhances platelet aggregation and TXA2 formation, and stimulates platelet-endothelial cell interaction in rabbits. These effects are probably due to impaired NO elaboration, as indicated by decreased urinary nitrate excretion. Chronic dietary supplementation with L-arginine elevates systemic NO elaboration and significantly increases the PGI2/TXA2 ratio. It thus beneficially influences the homeostasis between vasodilator and vasoconstrictor prostanoids in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Diphosphate / pharmacology
  • Animals
  • Aorta
  • Arginine / administration & dosage*
  • Arginine / blood
  • Biomarkers / urine
  • Creatinine / urine
  • Diet*
  • Endothelium, Vascular / drug effects
  • Epoprostenol / urine
  • Gas Chromatography-Mass Spectrometry
  • Hypercholesterolemia / blood
  • Hypercholesterolemia / metabolism*
  • In Vitro Techniques
  • Male
  • Nitrates / urine
  • Nitroprusside / pharmacology
  • Platelet Aggregation*
  • Rabbits
  • Thromboxane A2 / biosynthesis*
  • Thromboxane B2 / analogs & derivatives
  • Thromboxane B2 / urine
  • Vasodilator Agents / pharmacology

Substances

  • Biomarkers
  • Nitrates
  • Vasodilator Agents
  • Nitroprusside
  • Thromboxane B2
  • Thromboxane A2
  • Adenosine Diphosphate
  • 2,3-dinor-thromboxane B2
  • Arginine
  • Creatinine
  • Epoprostenol