1. L-Arginine is the physiological precursor of nitric oxide which induces 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 placebo on blood pressure, heart rate and peripheral haemodynamics in ten healthy male subjects. Cyclic GMP, NO−2 and NO−3 were determined in plasma and urine to assess NO production in vivo by a new, highly specific and sensitive gas chromatography-mass spectrometry method.
3. L-Arginine significantly decreased mean arterial blood pressure and increased heart rate. The effect was more pronounced on diastolic than on systolic blood pressure. This was due to a decreased peripheral arteriolar resistance, as in femoral artery Doppler sonography the arterial diameter was unchanged but blood flow was increased. These haemodynamic effects were not observed after placebo administration.
4. Urinary excretion of cyclic GMP increased by 65.4% after L-arginine and by 25.1% after placebo. Urinary NO−2 excretion was near the threshold of detection. Urinary NO−3 excretion increased by 79.7% after L-arginine. Plasma arginine levels increased nearly ten-fold after the L-arginine infusion, and plasma cyclic GMP increased by a similar rate as in urine. However, plasma NO−2 and NO−3 remained unchanged after both treatments, as did plasma α-atrial natriuretic peptide levels.
5. Platelet aggregation was inhibited by 32.7% after L-arginine (P < 0.05), but was unchanged after placebo. Platelet intracellular cyclic GMP was increased by 43.0% after L-arginine, but not after placebo (P < 0.05).
6. We conclude that intravenous L-arginine decreases peripheral arteriolar tone and inhibits platelet aggregation in healthy human subjects by enhancing nitric oxide formation and, concomitantly, cyclic GMP formation.