L-arginine modulates aggregation and intracellular cyclic 3 ',5 '-guanosine monophosphate levels in human platelets: Direct effect and interplay withantioxidative thiol agent

Platelet nitric oxide is involved in the control of aggregability via cycli c 3',5'-guanosine monophosphate synthesis. Since L-arginine provides a guan idino nitrogen group for nitric oxide synthesis through nitric oxide syntha se activity, we tried to clarify whether an increased availability of this amino acid can directly modulate the response of human platelets, In our co nditions, L-arginine (at 10-6000 mu mol/L) was able to influence the respon se of human platelets stimulated with adenosine 5-diphosphate and collagen both in PRP and in whole blood. The anti-aggregating effect was not present when D-arginine was used. Permeabilized platelets exhibited an increased s ensitivity to L-arginine, Also, an increased availability of Ca2+ enhanced L-arginine effect. L-arginine (at 120-500 mu mol/L) increased cyclic 3',5'- guanosine monophosphate levels in resting platelets; the amino acid also de termined an increase of cyclic 3',5'-guanosine monophosphate in platelets a t the end of adenosine 5-diphosphate-induced aggregation. Nitric oxide synt hase inhibitor N-G-monomethyl-L-arginine prevented L-arginine effects on ag gregation and cyclic 3',5'-guanosine monophosphate synthesis. Phosphodieste rase III inhibitor milrinone and antioxidative thiol N-acetyl-L-cysteine en hanced the effect of L-arginine on cyclic 3',5'-guanosine monophosphate. In conclusion, L-arginine exerts inhibitory effects on human platelet respons e through a nitric oxide-dependent synthesis of cyclic 3',5'-guanosine mono phosphate, A positive interplay on platelet response between L-arginine and milrinone or antioxidative thiol N-acetyl-L-cysteine was evidenced. (C) 19 99 Elsevier Science Ltd. All rights reserved.