Evidence that the rat is not an appropriate model to study the role of prostaglandins in normal or abnormal platelet aggregation

Huzoor-Akbar,; Anwer, Khursheed

doi:10.1016/0049-3848(86)91701-9

Cited by 19 publications

(4 citation statements)

References 26 publications

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“…In contrast, the three cyclo-oxygenase inhibitors were completely ineffective. These results are in agreement with previous reports indicating that ASA is inactive in vitro and in vivo (3,29,30,31). This is not surprising because ADP-induced aggregation of rat platelets produces only a single aggregation wave, without production of TXA2, whatever the calcium concentration of the medium (1).…”

Section: Discussionsupporting

confidence: 94%

“…It is tempting to attribute this inhibition to blockade of endoperoxide or TXA2 synthesis. However, these substances (3,4), like their precursor arachidonic acid (2, 3), do not aggregate rat platelets at non-lytic concentrations. Nevertheless, it is possible that TXA2 formed upon collagen stimulation could act synergistically with released ADP (2), so that cyclo-oxygenase inhibition would block this potentiation.…”

Section: Discussionmentioning

confidence: 97%

“…Rat platelets for example, do not display the same reactivity to the main endogenous agonists: ADP induced only a single aggregation wave without TXA2 formation or serotonin and ADP release, whatever the calcium concentration of the medium (1). Arachidonic acid, at non-lytic concentrations (2,3) or even PGH2 (4) or a stable TXA2 analog (3) do not cause aggregation of rat platelet-rich plasma (PRP). Collagen induces rat platelet aggrega tion at somewhat higher concentrations than needed for human platelets (5).…”

Section: Introductionmentioning

confidence: 99%

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ADP Plays a Key Role in Thrombogenesis in Rats

et al. 1988

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SummaryThe relative importance of ADP, arachidonic acid metabolites and serotonin as thrombogenic factors was evaluated in rats by comparing, after oral administration, the effects of two inhibitors of ADP-induced platelet aggregation (ticlopidine and PCR 4099), three cyclo-oxygenase inhibitors (aspirin, triflusal and indobufen) and a selective serotonin 5HT2 receptor antagonist (ketanserin) on platelet aggregation, in four platelet-dependent thrombosis models and on bleeding time. Platelet aggregation induced by ADP and collagen was completely inhibited by ticlopidine and PCR 4099 whereas only the collagen aggregation was reduced by the cyclo-oxygenase inhibitors. Ketanserin or a depletion of platelet serotonin by reserpine did not affect platelet aggregation. Ticlopidine and PCR 4099 greatly prolonged rat tail transection bleeding time. This is probably related to their known ability to inhibit ADP-mediated platelet aggregation. In contrast, the cyclooxygenase inhibitors did not affect bleeding time at all. Reserpine and ketanserin prolonged bleeding time by interfering with the action of serotonin on the vascular wall. Ticlopidine and PCR4099 were very potent antithrombotics in all the models. Aspirin, only at a high dose, inhibited poorly thrombus formation on a silk thread in an arterio-venous shunt, suggesting that the inhibition of cyclo-oxygenase was not responsible. Triflusal was inactive in all models while indobufen slightly reduced thrombus formation in the silk thread and metallic coil models. Ketanserin and reserpine reduced thrombus only in the metallic coil model. Thrombus formation was greatly reduced in fawn-hooded rats, which lack ADP in their platelet dense granules because of a genetic storage pool deficiency. Taken together, the results obtained with the drugs and with the fawn-hooded rats support the concept that ADP plays a key role in thrombogenesis in rats.

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Section: Discussionsupporting

confidence: 94%

Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

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ADP Plays a Key Role in Thrombogenesis in Rats

et al. 1988

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“…Activation of platelets of these rat strains has been examined by different authors with inconsistent results regarding hypo-or hyperaggregability. [10][11][12][13][14][15][16] Because most of these results have been obtained from in vitro experiments, different methodology (washed platelet or platelets in plasma, different anticoagulants) may at least partially explain this discrepancy.…”

mentioning

confidence: 99%

Evidence from comparative investigations that impaired platelet activation is not specific for stroke-prone spontaneously hypertensive rats.

Klee¹,

Vater²,

Schmid‐Schönbein³

et al. 1993

Stroke

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Background and Purpose: Platelet behavior of Sprague Dawley (SD), Wistar (WI), Wistar-Kyoto (WKY), spontaneously hypertensive (SHR), and stroke-prone spontaneously hypertensive rats (SHRSP) was studied in vivo to evaluate the importance of hypertension-related hemostatic disorders.Methods: The study was based on the model of stimulus-induced pulmonary microembolization of labeled platelets. After injection of`tCr-labeled homologous platelets into urethane-anesthetized rats, the organ distribution of the platelets was continuously monitored by gamma detectors. Count rates of two detectors -one placed above the animals' thoraxes (Cl), the other above their abdomens (C2) -and the ratio of Cl: C2 were calculated. The following platelet activators were applied intravenously: adenosine diphosphate (ADP; 50 ,ug/kg), collagen (100 ,ug/kg), and thrombin (50 IU/kg).Results: All three substances caused a reversible pulmonary accumulation of the labeled platelets and hence an increase in C1/C2 (AC1/C2%). ADP induced a shift of 75% in SD, 52% in WI, 32% in WKY, 30% in SHR, and 31% in SHRSP. Thrombin-mediated shift was 79% in SD, 64% in WI, 58% in WKY, 48% in SHR, and 54% in SHRSP. Collagen induced a shift of 85% in SD, 96% in WI, 84% in WKY, 56% in SHR, and 62% in SHRSP.Conclusions: Because indistinguishable results were observed in both hypertensive strains, we conclude that impaired platelet aggregation is not specific for SHRSP. Hence, it may not primarily be responsible for the increased occurrence of stroke in these animals.

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Biochemistry of Altered Platelet Reactivity in Hypertension

Huzoor-Akbar

1999

Handbook of Platelet Physiology and Pharmacology

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Evidence that the rat is not an appropriate model to study the role of prostaglandins in normal or abnormal platelet aggregation

Cited by 19 publications

References 26 publications

ADP Plays a Key Role in Thrombogenesis in Rats

ADP Plays a Key Role in Thrombogenesis in Rats

Evidence from comparative investigations that impaired platelet activation is not specific for stroke-prone spontaneously hypertensive rats.

Biochemistry of Altered Platelet Reactivity in Hypertension

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