Yoshimoto H, Suehiro A, Kakishita E
Second Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
J Cardiovasc Pharmacol. 1999 Jan;33(1):109-15. doi: 10.1097/00005344-199901000-00016.
We examined the effect of NO on collagen-induced whole blood aggregation and platelet activation in whole blood by using impedance aggregometry and flow cytometry. For the extracellular generation of NO, we chose sodium nitroprusside dihydrate (SNP), and as intracellular generators of NO, L-arginine and isosorbide dinitrate (ISDN). The latter two significantly inhibited whole blood aggregation, whereas SNP had no such effect. The inhibitory effect of ISDN was diminished by addition of methylene blue (MB) or 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-l-oxyl 3-oxide (carboxyl-PTIO), and the inhibitory effect of L-arginine was diminished by addition of N(G)-monomethyl-L-arginine monoacetate (L-NMMA). Although the addition of ISDN increased the cyclic guanosine monophosphate (cGMP) level in whole blood and in the suspension of platelets and white blood cells (PLTs + WBCs), no increase was found in platelet-rich plasma (PRP). The P-selectin expression on the platelet surface in whole blood was reduced by ISDN and L-arginine. These findings suggest that the intracellular generation of NO inhibits whole blood aggregation, and this mechanism may play an important role in its antithrombotic effect in whole blood.
我们通过使用阻抗聚集测定法和流式细胞术，研究了一氧化氮（NO）对胶原蛋白诱导的全血聚集及全血中血小板活化的影响。对于细胞外NO的产生，我们选用了二水合硝普钠（SNP），而作为细胞内NO的产生剂，我们选用了L-精氨酸和异山梨醇二硝酸酯（ISDN）。后两者显著抑制全血聚集，而SNP则无此作用。加入亚甲蓝（MB）或2-(4-羧基苯基)-4,4,5,5-四甲基咪唑啉-1-氧基3-氧化物（羧基-PTIO）后，ISDN的抑制作用减弱；加入N(G)-单甲基-L-精氨酸单乙酸酯（L-NMMA）后，L-精氨酸的抑制作用减弱。尽管加入ISDN可使全血以及血小板和白细胞悬液（PLTs + WBCs）中的环磷酸鸟苷（cGMP）水平升高，但在富血小板血浆（PRP）中未发现升高。ISDN和L-精氨酸可降低全血中血小板表面P-选择素的表达。这些发现表明，细胞内产生的NO可抑制全血聚集，且该机制可能在其对全血的抗血栓形成作用中发挥重要作用。
