A study of intravascular platelet aggregation by continuous platelet counting

A non‐invasive technique for the scintigraphic determination of 111indium‐labelled platelet aggregation stimulated with submaximal doses of adenosine diphosphate (ADP, 56 μg kg−1 i.v.), collagen (100 μg kg−1 i.v.), platelet‐activating factor (PAF, 0.1 μg kg−1 i.v.) or thrombin (18 iu kg−1 i.v.) was used to investigate the platelet‐inhibitory effects of endothelin 1 (ET‐1) in anaesthetized rabbits in vivo. ET‐1 (1 nmol kg−1 i.v.) inhibited ADP‐stimulated platelet aggregation in vivo; a maximum inhibition of 78% of the control value was reached at 3 min, with 45% inhibition at 15 min, and a return to control values at 30 min after injection of the peptide. ET‐1 (1 nmol kg−1 i.v.) inhibited in vivo platelet aggregation in response to collagen or PAF by 86% and 52%, respectively, but had no effect on thrombin‐induced platelet aggregation. Indomethacin (5 mg kg−1 i.v.) abolished the ET‐1‐induced inhibition of ADP‐stimulated platelet aggregation and significantly potentiated and prolonged the pressor response brought about by ET‐1. In conclusion, the data demonstrate that ET‐1 potently inhibits platelet aggregation in the anaesthetized rabbit in vivo by releasing a hypotensive and anti‐aggregatory cyclo‐oxygenase product, presumably prostacyclin, into the circulation.

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Endothelin‐1 inhibits platelet aggregation in vivo: a study with ¹¹¹indium‐labelled platelets

Thiemermann

May

Page

et al. 1990

“…A study of platelet aggregation in the absence of an anticoagulant would therefore be of interest. An in vivo technique using a modified Technicon Autocounter enables platelet aggregation to be studied in vivo without the interference of an anticoagulant (Smith & Freuler, 1973).…”

Section: Introductionmentioning

confidence: 99%

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

Mallarkey

Smith

1984

Self Cite

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.

“…The experiments were performed in anaesthetized rabbits which were challenged by intravenous injections ofcollagen. Drug effects on platelet aggregate formation were measured by continuous on-line platelet counting using a previously described technique (Smith & Freuler, 1973).…”

Section: 'Present Address: Department Of Pharmacology Medicalmentioning

confidence: 99%

In vivo interaction of prostacyclin with an inhibitor of cyclic nucleotide phosphodiesterase, HL 725

Darius

Lefer

Leprán

et al. 1985

1 Prostacyclin (PGI2) inactivates platelets by stimulation of adenylate cyclase, and its effect can be potentiated in vitro by simultaneous inhibition of cyclic AMP phosphodiesterase. 2 The interaction of synthetic PGI2 and the potent phosphodiesterase inhibitor HL 725 was studied in a model of systemic platelet activation by intravenous injection of collagen. Platelet aggregate formation was evaluated by continuous on-line measurement of the circulating platelet count. 3 Collagen injection in rabbits receiving vehicle caused a 30 3% decrease in the circulating platelet count. Infusion of PGI2 (0.05, 0.1 and 0.75 fg kg-' min-) dose-dependently inhibited this decrease. HL 725 (0.5, 1 and 3 Ag kg-l min-i) caused a slight but significant effect. 4 Combinations of PGI2 and HL725, respectively, at 0.25 + 1.0 and 0.1 + 0.5 tig kg-' min-' inhibited platelet aggregate formation to a greater extent than when either substance was used alone and produced a comparable inhibition to PGI2 at 0.75 ytg kg-' min-. 5 Collagen induced an acute fall in the mean arterial blood pressure (MABP) which also was inhibited by PGI2, HL 725 and their combinations. 6 The infusion of a combination of PGI2 and HL 725 before collagen produced a decrease in the MABP which was greater than when either compound was used on its own. 7 Thus, PGI2 and the phosphodiesterase inhibitor HL725 interact in vivo to inhibit platelet aggregation and lower MABP.