No abstract

The adhesion of thrombin-stimulated human blood platelets to either the endothelial surface of intact bovine aorta or cultured bovine aortic endothelial cells was studied to determine the role of endothelium-derived relaxing factor in the regulation of platelet adhesion. Endothelial cells and platelets were pretreated with indomethacin to prevent the formation of prostaglandins. The adhesion of thrombinstimulated platelets to endothelial cells was reduced by superoxide dismutase and bradykinin. The inhibitory effect of both drugs was abolished by hemoglobin and was absent in strips of bovine aorta where the endothelial cells had been removed by scraping. It is suggested that the effects of bradykinin are mediated by the release of endothelium-derived relaxing factor, which is protected from destruction by superoxide dismutase, and that endothelium-derived relaxing factor contributes to the nonadhesive properties of the vascular endothelium.Unstimulated or stimulated blood platelets do not easily adhere either to the intact endothelium (1) or to the surface of intact confluent monolayers of cultured endothelial cells (2)(3)(4). This nonthrombogenicity appears to be an intrinsic property of the endothelial cell (EC) plasma membrane. In addition to providing a physical barrier between the blood and thrombogenic subendothelial structures, ECs possess both anticoagulant and antiplatelet properties. The anticoagulant properties are expressed in (i) the synthesis and release of a heparin sulphate that promotes the ability of plasma antithrombin III to inactivate thrombin rapidly (5, 6), (ii) the production of thrombomodulin (7), and (iii) the synthesis of plasminogen activator (8). The antiplatelet properties of the EC surface have been variously attributed to (i) a netnegative charge on the endothelial surface (9), (ii) the presence of an ectoplasmic ATPase that metabolizes aggregatory nucleotides released from aggregating platelets (10), (iii) the synthesis and release of the antiaggregatory prostanoid prostacyclin (11), and (iv) the intracellular concentration of 13-hydroxyoctadecadienoic acid, a lipoxygenase product of linoleic acid (12). The relative contribution of these factors to the nonthrombogenic nature of the EC plasma membrane presently is unknown.Thromboresistance appears to be unrelated to prostacyclin release, since inhibition of prostacyclin production in cultured ECs does not increase the adhesion of either unstimulated or stimulated platelets (1, 3), although concentrations of prostacyclin higher than those normally released at the EC surface are highly effective in preventing platelet adhesion (1,3,4,13). In addition to releasing prostacyclin,

Superoxide dismutase (SOD, 60 u ml−1) or ferricytochrome c (70 μm) significantly inhibited thrombin‐stimulated platelet adhesion to gelatin‐coated plastic, whereas catalase (1000 u ml−1) or mannitol (1 mm) had no effect. The platelet aggregation induced by low concentrations of thrombin (causing less than 45% maximal change in light transmission) was inhibited by SOD. Catalase or mannitol had no effect on platelet aggregation. Pyrogallol (an O2− generator) enhanced both platelet adhesion to gelatin‐coated plastic and platelet aggregation induced by thrombin; this enhancement was neutralized by SOD. These results indicate that O2− increase both platelet adhesion and aggregation, whereas other free radicals such as hydrogen peroxide or hydroxyl radicals are not involved.

. The influence of sodium and potassium on the accumulation of 5‐hydroxytryptamine (5‐HT) by rat blood platelets was investigated. . An absolute dependence of 5‐HT uptake on the sodium concentration in the medium was found. . Removal of potassium reduced the uptake by about 60% High concentrations of potassium inhibited sodium‐dependent accumulation. . The observations have been discussed in terms of a carrier‐mediated transport process for 5‐HT operating in the platelet membrane.