Endogenous nitric oxide acts as a natural antithrombotic agent in vivo by inhibiting platelet aggregation in the pulmonary vasculature

Nitric oxide (NO) is a powerful vasodilator and an inhibitor of platelet ag gregation in vitro, While the ability of NO to modulate vascular tone in vi vo has been proven, only a few studies have assessed its platelet inhibitor y activity in vivo. We have employed two complementary animal models of pul monary platelet thromboembolism to assess the antithrombotic activity of en dogenous NO in vivo. The inhibition of nitric oxide synthase (NOS) by L-NAME significantly poten tiated while the administration of the NOS substrate L-arginine significant ly reduced the accumulation of In-111-labelled platelets in the pulmonary v asculature of rabbits induced by intravenous collagen plus epinephrine. L-N AME or L-arginine did not, however, modify (111)ln-labelled erythrocyte dis tribution in lungs and phenylephrine had no effect on platelet accumulation following collagen + adrenaline, suggesting that the effects of L-NAME wer e not due to vasoconstriction but rather to a direct modification of platel et function. In mice, L-NAME significantly reduced the dose of collagen + a drenaline required to induce thromboembolic mortality: increased the fall i n circulating platelets and increased the % of pulmonary vessels occluded b y platelet thrombi. The effects of L-NAME were reversed by L-arginine but n ot by a dose of nicardipine exerting maximal vasodilatation. Phenylephrine did not potentiate collagen + adrenaline-induced mortality. In the pulmonary vasculature in vivo, endogenous NO inhibits collagen t adr enaline-induced aggregation and enhances platelet disaggregation. This natu ral modulator function of NO is exerted via a direct effect on platelets an d not as a result of haemodynamic changes.