L-ARGININE INFUSION DECREASES PERIPHERAL ARTERIAL RESISTANCE AND INHIBITS PLATELET-AGGREGATION IN HEALTHY-SUBJECTS

1. L-Arginine is the physiological precursor of nitric oxide which ind uces vasodilatation and inhibits platelet aggregation by the formation of cyclic GMP. 2. In the present study we investigated the effects of an intravenous infusion of L-arginine (30 g, 30 min) compared with pl acebo on blood pressure, heart rate and peripheral haemodynamics in te n healthy male subjects. Cyclic GMP, NO2- and NO3- were determined in plasma and urine to assess NO production in vivo by a new, highly spec ific and sensitive gas chromatography-mass spectrometry method. 3. L-A rginine significantly decreased mean arterial blood pressure and incre ased heart rate. The effect was more pronounced on diastolic than on s ystolic blood pressure. This was due to a decreased peripheral arterio lar resistance, as in femoral artery Doppler sonography the arterial d iameter was unchanged but blood flow was increased. These haemodynamic effects were not observed after placebo administration. 4. Urinary ex cretion of cyclic GMP increased by 65.4% after L-arginine and by 25.1% after placebo. Urinary NO2- excretion was near the threshold of detec tion. Urinary NO3- excretion increased by 79.7% after L-arginine. Plas ma arginine levels increased nearly ten-fold after the L-arginine infu sion, and plasma cyclic GMP increased by a similar rate as in urine. H owever, plasma NO2- and NO3- remained unchanged after both treatments, as did plasma alpha-atrial natriuretic peptide levels. 5. Platelet ag gregation was inhibited by 32.7% after L-arginine (P < 0.05), but was unchanged after placebo. Platelet intracellular cyclic GMP was increas ed by 43.0% after L-arginine, but not after placebo (P < 0.05). 6. We conclude that intravenous L-arginine decreases peripheral arteriolar t one and inhibits platelet aggregation in healthy human subjects by enh ancing nitric oxide formation and, concomitantly, cyclic GMP formation .