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. Ž . Ž Methods: The urinary excretion rates of 2,3-dinor-6-keto-PGF major urinary metabolite of PGI and 2,3-dinor-TXB major urinary . N s 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-TXB 2 Ž . Ž excretion significantly increased in the cholesterol group p -0.05 , and endogenous NO formation measured as urinary nitrate . Ž . Ž . excretion decreased p -0.05 . Both parameters were significantly correlated with each other R s 0.48, p -0.01 . L-arginine partly restored urinary nitrate excretion and significantly reduced TXA production to values even below those in the control group 2 Ž . p -0.001 . Urinary 2,3-dinor-6-keto-PGF excretion increased in early hypercholesterolaemia and returned to control values in the 1a second half of the study period. The early increase in urinary 2,3-dinor-6-keto-PGF excretion was attenuated by L-arginine. Platelet 1a 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 TXA formation, and stimulates platelet-endothelial cell interaction 2 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 PGI rTXA ratio. It thus beneficially 2 2 influences the homeostasis between vasodilator and vasoconstrictor prostanoids in vivo. q 1998 Elsevier Science B.V.
