de Belder A J, MacAllister R, Radomski M W, Moncada S, Vallance P J
Department of Cardiology, King's College Hospital, Denmark Hill, London, United Kingdom.
Cardiovasc Res. 1994 May;28(5):691-4. doi: 10.1093/cvr/28.5.691.
Nitric oxide (NO) is a vasodilator and inhibitor of platelet function. The clinical use of NO donors as inhibitors of platelet activation is limited by their concomitant hypotensive effect. S-nitroso-glutathione (GSNO) has a significant antiplatelet effect at doses that cause only a small decrease in blood pressure in rats. The aim of this study was to examine the antiplatelet and vasodilator properties of this nitrosothiol in the human forearm.
Forearm blood flow was measured by forearm occlusion plethysmography in five healthy males. Ex vivo platelet aggregation to ADP was performed in a platelet ionised calcium lumi-aggregometer.
Intra-arterial infusion of GSNO (0.2, 1, and 5 nmol.min-1) resulted in inhibition of ADP (1-10 microM) induced platelet aggregation. This inhibition was submaximal for 0.2 and maximal for 1 and 5 nmol.min-1. However, the antiaggregatory effect observed at the lowest dose of GSNO was accompanied only by a threshold increase in forearm blood flow.
These results show that GSNO is more effective as an inhibitor of platelet activation than as a vasodilator, suggesting that it is possible to achieve selective antiplatelet and potentially antithrombotic effects with NO donors.
一氧化氮（NO）是一种血管舒张剂和血小板功能抑制剂。NO供体作为血小板活化抑制剂的临床应用受到其伴随的降压作用的限制。S-亚硝基谷胱甘肽（GSNO）在大鼠中仅引起血压小幅下降的剂量下具有显著的抗血小板作用。本研究的目的是研究这种亚硝基硫醇在人前臂中的抗血小板和血管舒张特性。
通过前臂阻断体积描记法测量5名健康男性的前臂血流量。在血小板离子钙发光聚集仪中进行离体血小板对ADP的聚集实验。
动脉内输注GSNO（0.2、1和5 nmol·min-1）导致对ADP（1-10 μM）诱导的血小板聚集的抑制。对于0.2 nmol·min-1，这种抑制作用是次最大的，而对于1和5 nmol·min-1是最大的。然而，在最低剂量的GSNO下观察到的抗聚集作用仅伴随着前臂血流量的阈值增加。
这些结果表明，GSNO作为血小板活化抑制剂比作为血管舒张剂更有效，这表明使用NO供体有可能实现选择性抗血小板和潜在的抗血栓形成作用。
