Prostanoid production in the presence of platelet activation in hypoxic cocaine-treated rats.
To extend our previous in vitro data, we investigated the effects of cocaine on thromboxane A2 (TXA2) and prostacyclin (PGI2) production in vivo in the rat. To obtain the slight platelet activation that our in vitro experiments showed useful to highlight the effect of cocaine, we infused cocaine in rats in the presence of platelet-activating factors (circulation of blood through a perspex vascular device or by infusion of sodium arachidonate) and in various respiratory conditions. Experiments were conducted in rats breathing atmospheric air (normoxic conditions) and in rats breathing an oxygen-poor mixture (hypoxic conditions). In rats under hypoxic conditions cocaine invariably increased TXA2 plasma levels, whereas in normoxic conditions it increased TXA2 only in the presence of platelet-activating factors. Cocaine significantly increased PGI2 plasma levels in arachidonate-treated rats in hypoxic respiratory conditions; in normoxic conditions cocaine left PGI2 levels unchanged. These results support the hypothesis that in cocaine users who have concomitant pathological conditions able to activate platelets, such as atherosclerosis, coronary vasospasm or ischaemia, or both, cocaine may contribute to the onset of thrombotic phenomena by interfering with the prostaglandin system.
Togna
G
G
Institute of Medical Pharmacology, University of Rome La Sapienza, Italy.
Graziani
M
M
Sorrentino
C
C
Caprino
L
L
D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D001800:Blood Specimen Collection / Q000295:instrumentation; D002339:Carotid Arteries; D003042:Cocaine / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D011464:Epoprostenol / Q000096:biosynthesis*; D000860:Hypoxia / Q000097:blood*; D008297:Male; D015539:Platelet Activation / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013928:Thromboxane A2 / Q000096:biosynthesis*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D014662:Vasoconstrictor Agents; D016718:Arachidonic Acid; D013928:Thromboxane A2; D011464:Epoprostenol; D003042:Cocaine