Platelet responsiveness and biosynthesis of thromboxane and prostacyclin in response to in vitro cocaine treatment.

Preincubation of rabbit platelet-rich plasma with cocaine hydrochloride, at low and high concentrations, increased the platelet responsiveness to arachidonic acid, in terms of the aggregating response and the thromboxane production. The thromboxane levels released by collagen-stimulated platelets were increased after incubation with low concentrations of cocaine, while marked decreases were observed after incubation with high doses of cocaine. No effects on platelet aggregation induced by collagen and ADP were observed when low concentrations of cocaine were added; on the other hand, high doses of the anaesthetic were found to block the aggregating effects of these two agents. Specific studies showed cocaine to have an inhibitory activity on prostacyclin release when the aortic tissue was mechanically and thermically stimulated. By contrast, the prostacyclin synthesis by 'exhausted' aortic rings incubated with arachidonic acid appeared to be enhanced after addition of cocaine. These results lead us to believe that cocaine modifies both the Ca++ membrane binding and the extent of Ca++ influx, thereby increasing the permeability to arachidonic acid and altering the affinity of the membrane binding sites for the aggregating agents.

Inhibition of aortic vessel adenosine diphosphate degradation by cadmium and mercury.

The effects of cadmium and mercury on ADP breakdown by vessel walls were investigated. These metals reduce the ADP clearance promoted by arterial tissue. This effect could be attributed to the inhibition of vessel wall ADP-ase enzyme, which plays an important role in the genesis of thrombotic phenomena.

In vitro effects of mercury on platelet aggregation, thromboxane and vascular prostacyclin production.

Mercuric chloride [25-50 micrograms/ml platelet-rich plasma (PRP)] lowers the threshold concentration of arachidonic acid (AA) required for triggering rabbit platelet aggregation and causes a marked increase of thromboxane production. The metal, added as HgCl2, does not modify (50 micrograms/ml PRP) or block (100 micrograms/ml PRP) the platelet aggregation wave induced by a normal aggregating dose of AA. Whether or not AA-induced platelet aggregation takes place, a large increase in thromboxane production is observed. Methyl mercury, assayed as reference drug, induces platelet aggregation and a significant increase of thromboxane levels. Finally, HgCl2 and methyl mercury, in a concentration range of 0.125-0.5 micrograms/microliters in the incubation liquid, induce an increased prostacyclin release from rat aortic tissue.