HEMODYNAMIC AND BIOCHEMICAL RESPONSES TO L-ARGININE AND L-LYSINE INFUSIONS IN NORMAL SUBJECTS - L-ARGININE-INDUCED VASODILATATION CANNOT BEEXPLAINED BY NONSPECIFIC EFFECTS OF CATIONIC AMINO-ACIDS

1. Pharmacological stimulation of the synthesis of nitric oxide (NO) m ay be important in the prevention or treatment of cardiovascular disea ses. 2. There is much discussion as to whether the precursor of NO, L- arginine, is able to stimulate basal endothelial NO production. L-Argi nine is known to have vasodilating effects. However, it is not clear w hether L-arginine-induced vasodilatation is attributable to an increas e in NO production or to other systemic effects of L-arginine. 3. To i nvestigate further the mechanisms of the L-arginine-induced vasodilata tion, we compared the responses to L-arginine with those to saline and L-lysine in healthy subjects, L-Lysine is not a substrate for NO synt hesis, but shares many of L-arginine's other properties. 4. During L-a rginine infusion, blood pressure decreased [systolic blood pressure fr om 120.2 (SD 8.8) to 117.3 (12.l) mmHg (P=0.05); diastolic blood press ure fi om 65.3 (5.9) to 61.6 (7.9) mmHg (P<0.01)], and heart rate and extracellular fluid volume increased. The total peripheral vascular re sistance decreased during L-arginine infusion by 18.0 (11.4)% (P less than or equal to 0.05 compared with baseline and compared with L-lysin e infusion). These results indicate vasodilatation. No changes were ob served during L-lysine and saline infusion.5. Plasma cyclic GMP (the s econd messenger for NO) increased during L-arginine but also during L- lysine infusion [from 5.7 (1.2) to 6.8 (1.7) nmol/l (P<0.01), and from 5.8 (1.8) to 7.0 (2.9)nmol/l (P<0.05) respectively], Plasma L-citrull ine (a by-product of NO synthesis from L-arginine) increased during L- arginine infusion from 30.6 (7.5) to 47.1 (9.9)mu mol/l (P<0.001), but also during L-lysine infusion from 32.7 (6.5) to 42.0 (83) mu mol/l ( P<0.001). 6. Plasma electrolytes and atrial natriuretic peptide concen trations responded similarly to L-arginine and L-lysine infusion, indi cating similar effects on osmolality, plasma volume expansion and pota ssium distribution. 7. In conclusion, although L-lysine infusion had e ffects that were similar to those of L-arginine infusion, no vasodilat ation was observed. Therefore, these effects cannot account for the L- arginine-induced vasodilatation. This finding indirectly supports the hypothesis that the vasodilatation during L-arginine infusion might be mediated by an increase in NO synthesis. If so, our data suggest that the presumed markers for NO synthesis, plasma cyclic GMP and L-citrul line concentrations, do not accurately reflect this increase. Instead, the rise in plasma cyclic GMP may be related to the rise in ANP The r ise in L-citrulline may be related to competition with L-arginine for the same cell membrane transport mechanism and to stimulation of the u rea cycle.