In vivo platelet aggregation in the rat: dependence on extracellular divalent cation and inhibition by nonsteroidal anti‐inflammatory drugs

Abstract

Using the Technicon Autocounter, the mechanisms involved in collagen‐induced platelet aggregation in vivo have been studied without the interference of an anticoagulant. Extracellular divalent cation was essential for in vivo platelet aggregation. Non‐steroidal anti‐inflammatory drugs completely inhibited the aggregation induced by collagen in platelet‐rich plasma in in vitro or ex vivo studies. In vivo only a maximum of 50% inhibition was achieved when release of thromboxane A2 (TXA2) was completely inhibited. Therefore in vivo, collagen causes aggregation through more than one pathway which operate independently of each other and which are all dependent on extracellular divalent cation. In vivo, when different doses of collagen were compared, aggregation produced by low doses of collagen was more dependent upon prostaglandin endoperoxide/TXA2 formation.

Involvement of 5-Hydroxytryptamine in Platelet Aggregation In Vivo in Rats and Guinea Pigs

“…5). As shown in previous papers indomethacin 4 mg/kg produced a 40% inhibition of collagen-induced fall in platelet count (7,13). The simultaneous injection of indometha cin 4 mg/kg and ketanserin 4 mg/kg produced a smaller fall which was not significantly different from the responses obtained with indomethacin alone.…”

“…5-HT may be released slowly to maintain the haemostatic and thrombogenic activity of platelets. Previous studies in this laboratory have shown that the inhibition of TxA2 by cyclooxygenase inhibitors or blocking of thromboxane recep tors with EP 045 and EP 092 only produced a 30-40% inhibition of collagen-induced aggregation (7,13,14). The question remains which aggregating agent is responsible for the 60-70% of collagen-induced aggregation in rats.…”

“…In other species, platelet activating factor (PAF) is also involved in collagen-induced platelet aggregation (6). Mallarkey and Smith (7) showed that platelet activation in vivo was dependent on extracellular divalent cation.…”

A comparative study of the involvement of the prostaglandin H2/thromboxane A2 pathway in intravascular platelet aggregation in guinea‐pigs and rats

“…Previous work has shown that the modified Technicon Autocounter (Smith & Freuler, 1973) can be used for studying intravascular platelet aggregation where the collagen-induced fall in platelet count can be monitored continuously without the use of an intravenous anticoagulant (Smith, 1981). When this technique was used in the rat it appeared that extracellular divalent cation is essential for normal intravascular platelet aggregation, that the endoperoxide/thromboxane pathway is responsible for part of the aggregation response and that the involvement of this pathway is dependent upon the amount of collagen exposed to the platelets (Mallarkey & Smith, 1984a).…”