Endogenous nitric oxide protects against thromboembolism in venules but not in arterioles.
Because nitric oxide (NO) inhibits aggregation and adhesion of blood platelets, NO may play a role in platelet-vessel wall interactions. Therefore, the purpose of this study was to investigate the involvement of endogenous NO in thromboembolic processes, as induced by wall puncture, in rabbit mesenteric arterioles and venules (diameters 20 to 43 microm). In venules, inhibition of NO synthase by superfusion of the mesentery with N omega-nitro-L-arginine (L-NA; 0.1 mmol/L) significantly increased the duration of embolization (from 50 seconds to 511 seconds) and the number of emboli produced (from 2 to 11 emboli per vessel), while the median period of time needed to produce an embolus was not influenced. On the contrary, in arterioles, L-NA had no significant effect on embolization (duration of embolization: 426 seconds in the control 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 to the L-NA superfusate of the exogenous NO donor sodium nitroprusside (0.1 micromol/L) also resulted in reversal of the L-NA effects in venules, while in arterioles, it slightly but significantly decreased embolization duration. The differences in effect of L-NA on embolization between arterioles and venules were not caused by differences in fluid dynamic conditions. It is concluded that the role of endogenous NO in inhibiting thromboembolic processes is more important in venules than in arterioles.
Broeders
M A
MA
Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, The Netherlands.
Tangelder
G J
GJ
Slaaf
D W
DW
Reneman
R S
RS
oude Egbrink
M G
MG
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001160:Arterioles / Q000293:injuries*; D005260:Female; D008297:Male; D018715:Microscopy, Video; D009569:Nitric Oxide / Q000502:physiology*; D019335:Nitroarginine / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D011817:Rabbits; D012421:Rupture / Q000517:prevention & control; D013923:Thromboembolism / Q000517:prevention & control*; D014699:Venules / Q000293:injuries*
D009599:Nitroprusside; D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine