BACKGROUND Endothelial dysfunction plays a key role in the aging process and in the development of cardiovascular diseases. Endothelial function is associated with the availability of nitric oxide, produced in endothelial cells from L-arginine. We aimed to study the effect of L-arginine on the function of the cardiovascular system, and to determine whether its use can improve endothelial function, which could be beneficial in preventing the formation and development of cardiovascular diseases in trained and sedentary subjects. METHODS Measurement were performed in healthy normotensive men, divided into four groups, according to age and physical activity: 12 young sedentary (YS), mean age 23,5 ± 2,4) and age matched trained (YT) (N=18); 11 elder sedentary (ES) (mean age 45,7 ± 7,5) and age matched trained subjects (ET) (N=12). Cardiovascular parameters were measured at rest with the Task Force Monitor device. Laser Doppler (LD) fluxmetry was used to measure skin LD flux on the forearm, before and after administration of 0.9 g L-arginine. Endothelium-dependent vasodilation was assessed by ACh iontophoresis and endothelium-independent vasodilatation with NaNP iontophoresis. RESULTS After ingestion of L-arginine the heart rate in all four groups statistically significantly decreased (YS 70.4 ± 4.2 vs. 66.3 ± 3.3; YT 62.1 ± 2.7 vs. 58.3 ± 2.0; ES 69.6 ± 3.2 vs. 62.7 ± 2.7; ET 58.0 ± 1.8 vs. 53.6 ± 1.2 beats/min) (paired t-test, p<0.05). The cardiac output decreased in three groups except in YS subjects (YT 7.04 ± 0.4 vs. 6.32 ± 0.3; ES 6.95 ± 0.5 vs. 5.9 ± 0.4; ET 7.08 ± 0.6 vs. 6.58 ± 0.4 L/min (paired t-test, p<0.05). The systolic (126.3 ± 4.1 vs. 120.0 ± 3.2 mmHg) and diastolic pressure (77.6 ± 2.5 vs. 74.3 ± 1.9mmHg) (paired t-test, p<0.05) decreased and LD flux at rest (9.3 ± 2.5 vs. 12.5 ± 1.3 PU) (paired t-test, p<0.05) increased in the ES group. After ingestion of L-arginine the endothelium-dependent vasodilation (73.4 ± 4.2 vs. 96.0 ± 9.5 PU) (Dunnett’s, p<0.05) improved only in the group of YT subjects. Endothelium-independent vasodilation was not altered in any of the groups. CONCLUSIONS The systemic effect of L-arginine was observed. In contrast, the expected improvement of endothelium-dependent vasodilation in elderly subjects was not found. Improved endothelium-dependent vasodilation in response to L-arginine in young trained subjects could justify the use of dietary L-arginine supplementation in athletes. Unresponsive endothelium-independent vasodilation in all groups confirms that the normal function of endothelial cells is necessary for the synthesis of nitric oxide from L-arginine. Additional studies are required for the final assessment of the impact of L-arginine on the formation and development of cardiovascular diseases.