ENDOGENOUS NITRIC-OXIDE PROTECTS AGAINST THROMBOEMBOLISM IN VENULES BUT NOT IN ARTERIOLES

Because nitric oxide (NO) inhibits aggregation and adhesion of blood p latelets, NO may play a role in platelet-vessel wall interactions. The refore, the purpose of this study was to investigate the involvement o f endogenous NO in thromboembolic processes, as induced by wall punctu re, in rabbit mesenteric arterioles and venules (diameters 20 to 43 mu m). In venules, inhibition of NO synthase by superfusion of the mesen tery with N-omega-nitro-L-arginine (L-NA; 0.1 mmol/L) significantly in creased the duration of embolization (from 50 seconds to 511 seconds) and the number of emboli produced (from 2 to 11 emboli per vessel), wh ile the median period of time needed to produce an embolus was not inf luenced. On the contrary, in arterioles, L-NA had no significant effec t on embolization (duration of embolization: 426 seconds in the contro l and 382 seconds in the L-NA group, with 20 and 12 emboli per vessel, respectively). Addition to the L-NA superfusate of L-arginine (L-ARG; 1 mmol/L), the active precursor for endogenous NO synthesis, resulted in a complete reversal of the L-NA effects in venules, while addition of the inactive D-arginine (D-ARG; 1 mmol/L) had no effect. Addition of L-ARG and D-ARG had no significant effect in arterioles. Addition t o the L-NA superfusate ofthe exogenous NO donor sodium nitroprusside ( 0.1 mu mol/L) also resulted in reversal of the L-NA effects in venules , while in arterioles, it slightly but significantly decreased emboliz ation duration. The differences in effect of L-NA on embolization betw een arterioles and venules were not caused by differences in fluid dyn amic conditions. It is concluded that the role of endogenous NO in inh ibiting thromboembolic processes is more important in venules than in arterioles.