A Study of Intravascular Platelet Aggregation in the Rat

1979 ◽  
Author(s):  
G. G. Duncan ◽  
G. M. Smith
Keyword(s):  
Arachidonic Acid ◽  
Platelet Count ◽  
Platelet Aggregation ◽  
Thromboxane A2 ◽  
Adenosine Diphosphate ◽  
Residual Response ◽  
Induced Aggregation ◽  
Anaesthetized Rat

Intravascular platelet aggregation can be studied by measuring the fall in the circulating platelet count induced by aggregating agents in anaesthetized animals. The Technicon Auto-counter was modified and connected via a double cannula to an anaesthetized rat to give a continuous count of the number of circulating platelets (1). Adenosine diphosphate (ADP), Collagen, Arachidonic acid (AA) and 5-Hydroxytryptamine (5-HT) were given at 15 minute intervals over a period of 2-3 hours. Aspirin (10 mg/Kg IV ) and Indomethacin (1-8 mg/Kg IV) partially inhibited collagen-induced aggregation and Indomethacin (2 mg/Kg IV) completely inhibited AA-induced aggregation. Adenosine (0.25 mg/min) inhibited the ADP-induced aggregation but did not inhibit aggregation produced by collagen or the residual response to collagen that remains after the addition of indomethacin.Reproducible responses to ADP and collagen were obtained but responses to AA and 5-HT were not reliable. Collagen-induced aggregation is thought to be mediated by the liberation of ADP, 5-HT and the formation of prostaglandin (PG ) endoperoxides and thromboxane A2. This study has shown that collagen-induced aggregation is reduced by inhibition of PG synthesis but the involvement of ADP or 5-HT could not be shown.

Effect of Picotamide on Platelet Aggregation and on Thromboxane A2 Production In Vivo

1991 ◽  
Vol 65 (03) ◽  
pp. 312-316 ◽  
Author(s):  
P Minuz ◽  
C Lechi ◽  
E Arosio ◽  
P Guzzo ◽  
M Zannoni ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Single Dose ◽  
Platelet Aggregation ◽  
Urinary Excretion ◽  
Ex Vivo ◽  
Thromboxane A2 ◽  
Normal Subjects ◽  
Dose Aspirin ◽  
Induced Aggregation

SummaryEffects of picotamide (900 mg in 3 oral administrations for 7 days) on ex vivo and in vivo platelet T×A2 production and on platelet aggregation wpre evaluated in 8 patients with peripheral arteriopathy and in 8 normal subjects. Picotamide significantly reduced ADP-induced platelet aggregation, but had no effect on that induced by arachidonic acid or the thromboxane analogue U46619. Though ex vivo platelet T×A2 production (T×B2 concentration after arachidonic-acid-induced aggregation) was reduced from 946 ± 141 (mean ± SD) to 285 ± 91 ng/ml in controls and from 1515 ± 673 to 732 ± 420 ng/ml in patients with arteriopathy, there was no effect on urinary excretion of 2,3-dinor-T×B2 (in vivo indicator of platelet T×A2 production), or on in vivo PGI2 production (urinary excretion of 6-keto-PGF1α and 2,3-dinor-6-keto-PGF1α). In the same subjects, single-dose aspirin reduced ex vivo T×B2 production by at least 98% and 2,3-dinor-T×B2 excretion from 116.7 ± 61.4 to 32.6 ± 17.0 nglg creatinine in control subjects, and from 156.3 ± 66.1 to 59.1 ± 19.2 ng/g creatinine in patients with peripheral arteriopathy. Our data suggest that inhibition of platelet T×A2 production in vivo may not be picotamide’s main mechanism of action.

Effects of Methylprednisolone and Hydrocortisone on Aggregation of Rabbit Platelets Induced by Arachidonic Acid and Other Aggregating Substances

1981 ◽  
Vol 46 (04) ◽  
pp. 676-679 ◽  
Author(s):  
Frank Glass ◽  
Howard Lippton ◽  
Philip J Kadowitz
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Platelet Rich Plasma ◽  
Adenosine Diphosphate ◽  
Actual Mechanism ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
The Difference ◽  
Induced Aggregation ◽  
Dose Dependent

SummaryThe effects of methylprednisolone and hydrocortisone on platelet aggregation induced by arachidonic acid (AA), collagen, adenosine diphosphate (ADP), prostaglandin (PG) H2, and a stable PGH2 analog, were studied in platelet-rich plasma (PRP) from the rabbit. Incubation of either steroid in PRP inhibited AA-, collagen- and ADP-induced platelet aggregation in a concentration-related manner. The dose of methylprednisolone required to inhibit 0.02 mM AA-induced aggregation was lower than that required to inhibit either 0.08 μg/ml collagen or 0.2 μM ADP-induced aggregation. Methylprednisolone produced a dose dependent inhibition of platelet aggregation induced by PGH2 and the stable PGH2 analog. In washed platelets methylprednisolone was more effective in inhibiting AA-induced aggregation than ADP- or collagen-induced aggregation; however, the difference in effect was less than in PRP. Platelet responses to AA in PRP from rabbits treated with hydrocortisone or methylprednisolone, 100 mg/kg i.v., were inhibited in a transient manner, whereas aggregation induced by ADP under similar conditions was unchanged. Since inhibition of aggregation elicited by AA occurred at concentrations which do not influence PGH2-, PGH2 analog-, collagen- or ADP-induced aggregation, the present data suggest that the steroids may inhibit the incorporation, the release, or the metabolism of arachidonic acid in platelets. The actual mechanism of this relatively specific inhibition of AA-induced aggregation by anti-inflammatory steroids is uncertain but may be related to the membrane “stabilizing” properties of methylprednisolone and hydrocortisone.

Adenosine diphosphate (ADP)–induced thromboxane A2generation in human platelets requires coordinated signaling through integrin αIIbβ3 and ADP receptors

Blood ◽  
2002 ◽  
Vol 99 (1) ◽  
pp. 193-198 ◽  
Author(s):  
Jianguo Jin ◽  
Todd M. Quinton ◽  
Jin Zhang ◽  
Susan E. Rittenhouse ◽  
Satya P. Kunapuli
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Thromboxane A2 ◽  
Adenosine Diphosphate ◽  
Dependent Manner ◽  
P2 Receptor ◽  
Concentration Dependent Manner ◽  
Fibrinogen Receptor ◽  
Adp Receptors ◽  
Inside Out

Adenosine diphosphate (ADP) is a platelet agonist that causes platelet shape change and aggregation as well as generation of thromboxane A2, another platelet agonist, through its effects on P2Y1, P2Y12, and P2X1 receptors. It is now reported that both 2-propylthio-D-βγ-dichloromethylene adenosine 5′-triphosphate (AR-C67085), a P2Y12 receptor–selective antagonist, and adenosine-2′-phosphate-5′-phosphate (A2P5P), a P2Y1 receptor–selective antagonist, inhibited ADP-induced thromboxane A2 generation in a concentration-dependent manner, indicating that coactivation of the P2Y12 and P2Y1 receptors is essential for this event. SC49992, a fibrinogen receptor antagonist, blocked ADP-induced platelet aggregation and thromboxane A2 production in a concentration-dependent manner. Similarly, P2 receptor antagonists or SC49992 blocked ADP-induced arachidonic acid liberation. Whereas SC49992 blocked arachidonic acid–induced platelet aggregation, it failed to inhibit thromboxane A2 generation induced by arachidonic acid. Thus, ADP-induced arachidonic acid liberation, but not subsequent conversion to thromboxane A2, requires outside-in signaling through the fibrinogen receptor. The Fab fragment of ligand-induced binding site–6 (LIBS6) antibody, which induces a fibrinogen-binding site on the integrin αIIbβ3, caused both platelet aggregation and thromboxane A2 generation. Inhibitors of phosphoinositide 3-kinase, Syk, Src kinases, or protein tyrosine phosphatases inhibited platelet aggregation but not thromboxane A2 generation, indicating that these signaling molecules have no significant role in phospholipase A2 activation. In the presence of P2 receptor antagonists A2P5P or AR-C67085, LIBS6 failed to generate thromboxane A2, suggesting that inside-out signaling through ADP receptors is necessary for this event. It was concluded that both outside-in signaling from the fibrinogen receptor and inside-out signaling from the P2Y1 and P2Y12 receptors are necessary for phospholipase A2 activation, resulting in arachidonic acid liberation and thromboxane A2 generation.

Inhibitory effects of H2-receptor antagonists on platelet function in vitro

1999 ◽  
Vol 18 (8) ◽  
pp. 487-492 ◽  
Author(s):  
K Nakamura ◽  
H Kariyazono ◽  
T Shinkawal ◽  
T Yamaguchi ◽  
T Yamashita ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Platelet Function ◽  
Chemical Structure ◽  
Adenosine Diphosphate ◽  
Imidazole Ring ◽  
Inhibitory Effects ◽  
Receptor Antagonists ◽  
Induced Aggregation

1 To evaluate in vitro inhibitory effects of four types of histamine H2-receptor antagonist (H2-receptor antagonists), famotidine, roxatidine, cimetidine and ranitidine, on platelet function, we examined aggregating potency and P-selectin levels with agonist-induced aggregation. Ranitidine and cimetidine inhibited, in concentration of 0.35 mM, the secondary aggregation induced by 5 pM adenosine diphosphate (ADP), the aggregation induced by 1,g/mL collagen and 3 gM arachidonic acid. All of H2-receptor antagonists inhibited, in concentration of 1.4 mm, the aggregation induced by ADP, collagen and arachidonic acid. Ranitidine and cimetidine reduced markedly, in same concentration, P-selectin levels after induction of aggregation by 5 gm ADP, 1 ig/xmL collagen and 3 gM arachidonic acid. When classified by the strength of inhibitory action, ranitidine and cimetidine were strong, followed by famotidine and roxatidine. 2 It is considered that inhibitory effects of H.-receptor antagonists on platelet function are weaker than those of acetylsalicylic acid (ASA), since ASA inhibited platelet aggregation in concentration of 100 MM. 3 No relationship was observed between inhibitory effects of H2-receptor antagonists on platelet aggregation induced by above agonists and the presence or absence of imidazole ring in the chemical structure.

Alteration of Platelet Aggregation by Cigarette Smoke and Carbon Monoxide

1982 ◽  
Vol 48 (03) ◽  
pp. 286-288 ◽  
Author(s):  
Ali Mansouri ◽  
Carol A Perry
Keyword(s):  
Carbon Monoxide ◽  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Cigarette Smoke ◽  
Adenosine Diphosphate ◽  
Second Phase ◽  
Aggregation Inhibition ◽  
Induced Aggregation

SummaryPlatelet aggregation with epinephrine, adenosine diphosphate and arachidonic acid was studied in the presence of cigarette smoke and carbon monoxide. It is shown that cigarette smoke inhibits the arachidonic acid induced platelet aggregation as well as the second phase of epinephrine induced aggregation. The adenosine diphosphate induced platelet aggregation is not significantly affected by cigarette smoke. Carbon monoxide causes similar alterations in platelet aggregation. These results suggest that cigarette smoke inhibits platelet aggregation. This aggregation inhibition is due to the presence of carbon monoxide.

Sevoflurane Inhibits Human Platelet Aggregation and Thromboxane A2Formation, Possibly by Suppression of Cyclooxygenase Activity

1996 ◽  
Vol 85 (6) ◽  
pp. 1447-1453. ◽  
Author(s):  
Hideo Hirakata ◽  
Fumitaka Ushikubi ◽  
Hiroshi Toda ◽  
Kumi Nakamura ◽  
Satoko Sai ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Human Platelet ◽  
Adenosine Diphosphate ◽  
Scatchard Analysis ◽  
Cyclooxygenase Activity ◽  
Human Platelet Aggregation ◽  
Induced Aggregation

Background Halothane increases bleeding time and suppresses platelet aggregation in vivo and in vitro. A previous study by the authors suggests that halothane inhibits platelet aggregation by reducing thromboxane (TX) A2 receptor-binding affinity. However, no studies of the effects of sevoflurane on platelet aggregation have been published. Methods The effects of sevoflurane, halothane, and isoflurane were examined at doses of 0.13-1.4 mM. Human platelet aggregation was induced by adenosine diphosphate, epinephrine, arachidonic acid, prostaglandin G2, and a TXA2 agonist ([+]-9, 11-epithia-11, 12-methano-TXA2, STA2) and measured by aggregometry. Platelet TXB2 levels were measured by radioimmunoassay, and the ligand-binding characteristics of the TXA2 receptors were examined by Scatchard analysis using a [3H]-labeled TXA2 receptor antagonist (5Z-7-(3-endo-([ring-4-[3H] phenyl) sulphonylamino-[2.2.1.] bicyclohept-2-exo-yl) heptenoic acid, [3H]S145). Results Isoflurane (0.28-0.84 mM) did not significantly affect platelet aggregation induced by adenosine diphosphate and epinephrine. Sevoflurane (0.13-0.91 mM) and halothane (0.49-1.25 mM) inhibited secondary platelet aggregation induced by adenosine diphosphate (1-10 microM) and epinephrine (1-10 microM) without altering primary aggregation. Sevoflurane (0.13 mM) also inhibited arachidonic acid-induced aggregation, but not that induced by prostaglandin G2 or STA2, although halothane (0.49 mM) inhibited the latter. Sevoflurane (3 mM) did not affect the binding of [3H]S145 to platelets, whereas halothane (3.3 mM) suppressed it strongly. Sevoflurane (0.26 mM) and halothane (0.98 mM) strongly suppressed TXB2 formation by arachidonic acid-stimulated platelets. Conclusions The findings that sevoflurane suppressed the effects of arachidonic acid, but not those of prostaglandin G2 and STA2, suggest strongly that sevoflurane inhibited TXA2 formation by suppressing cyclooxygenase activity. Halothane appeared to suppress both TXA2 formation and binding to its receptors. Sevoflurane has strong antiaggregatory effects at subanesthetic concentrations (greater than 0.13 mM; i.e., approximately 0.5 vol/%), whereas halothane has similar effects at somewhat greater anesthetic concentrations (0.49 mM; i.e., approximately 0.54 vol/%). Isoflurane at clinical concentration (0.84 mM; i.e., approximately 1.82 vol/%) does not affect platelet aggregation significantly.

Ticlopidine Facilitates the Deaggregation of Human Platelets Aggregated by Thrombin

1994 ◽  
Vol 71 (01) ◽  
pp. 091-094 ◽  
Author(s):  
M Cattaneo ◽  
B Akkawat ◽  
R L Kinlough-Rathbone ◽  
M A Packham ◽  
C Cimminiello ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Platelet Aggregation ◽  
Prostaglandin E1 ◽  
Human Platelet ◽  
Adenosine Diphosphate ◽  
Human Platelets ◽  
Before And After ◽  
Normal Human ◽  
Platelet Aggregates ◽  
Induced Aggregation

SummaryNormal human platelets aggregated by thrombin undergo the release reaction and are not readily deaggregated by the combination of inhibitors hirudin, prostaglandin E1 (PGE1) and chymotrypsin. Released adenosine diphosphate (ADP) plays an important role in the stabilization of thrombin-induced human platelet aggregates. Since ticlopidine inhibits the platelet responses to ADP, we studied thrombin-induced aggregation and deaggregation of 14C-serotonin-labeled platelets from 12 patients with cardiovascular disease before and 7 days after the oral administration of ticlopidine, 250 mg b.i.d. Before and after ticlopidine, platelets stimulated with 1 U/ml thrombin aggregated, released about 80–90% 14C-serotinin and did not deaggregate spontaneously within 5 min from stimulation. Before ticlopidine, hirudin (5× the activity of thrombin) and PGE1 (10 μmol/1) plus chymotrypsin (10 U/ml) or plasmin (0.06 U/ml), added at the peak of platelet aggregation, caused slight or no platelet deaggregation. After ticlopidine, the extent of platelet deaggregation caused by the same inhibitors was significantly greater than before ticlopidine. The addition of ADP (10 μmol/1) to platelet suspensions 5 s after thrombin did not prevent the deaggregation of ticlopidine-treated platelets. Thus, ticlopidine facilitates the deaggregation of thrombin-induced human platelet aggregates, most probably because it inhibits the effects of ADP on platelets.

Inhibition by Glaucocalyxin A of Aggregation of Rabbit Platelets Induced by ADP, Arachidonic Acid and Platelet-Activating Factor, and Inhibition of [3H]-PAF Binding

1992 ◽  
Vol 67 (04) ◽  
pp. 458-460 ◽  
Author(s):  
Zhang Bin ◽  
Long Kun
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Platelet Activating Factor ◽  
Northeastern China ◽  
Ethereal Extract ◽  
Ic50 Value ◽  
Rabbit Platelets ◽  
Ic50 Values ◽  
Induced Aggregation

SummaryGlaucocalyxin A is a new diterpenoid isolated from the ethereal extract of the leaves of Rabdosia japonica (Burm f) Hara var glaucocalyx (Maxim) Hara (Labiatae) collected in the northeastern China. When it was incubated with washed rabbit platelets, glaucocalyxin A inhibited ADP- or arachidonic acid-induced platelet aggregation with IC50 values of 4.4 μmol/1, 14.1 μmol/1 respectively. Glaucocalyxin A also inhibited PAF-induced aggregation of rabbit platelets which were refractory to ADP and arachidonic acid with an IC50 value of 13.7 μmol/1. Analysis of [3H]-PAF binding showed that glaucocalyxin A prevented [3H]-PAF binding to intact washed rabbit platelets with an IC50 value of 8.16 μmol/1, which was consistent with its inhibition of PAF-induced platelet aggregation.

Stimulated Platelet Aggregation, Thromboxane B2 Formation and Platelet Sensitivity to Prostacyclin - A Critical Evaluation

1981 ◽  
Vol 45 (03) ◽  
pp. 204-207 ◽  
Author(s):  
Wolfgang Siess ◽  
Peter Roth ◽  
Peter C Weber
Keyword(s):  
Arachidonic Acid ◽  
Platelet Count ◽  
Platelet Aggregation ◽  
Reliable Method ◽  
Platelet Rich Plasma ◽  
Critical Evaluation ◽  
Vascular Diseases ◽  
Thromboxane B2 ◽  
Test Time ◽  
Stimulation Of

SummaryPlatelets have been implicated in the development of atherosclerotic and thrombotic vascular diseases. Evaluation of platelet aggregation in relation to endogenously formed compounds which affect platelet function may provide information of clinical and pharmacological relevance. We describe a method in which thromboxane B2 (TXB2) formation was analyzed following stimulation of platelet-rich plasma (PRP) with ADP, 1-epinephrine, collagen, and arachidonic acid. In addition, we determined platelet sensitivity to prostacyclin following ADP- and collagen-induced platelet aggregation. The parameters under study were found to depend on the platelet count in PRP, on the type and dose of the aggregating agent used, and on the test time after blood sampling. By standardization of these variables, a reliable method was established which can be used in clinical and pharmacological trials.

Testosterone Potentiation of Ionophore and ADP Induced Platelet Aggregation : Relationship to Arachidonic Acid Metabolism

1981 ◽  
Vol 46 (02) ◽  
pp. 538-542 ◽  
Author(s):  
R Pilo ◽  
D Aharony ◽  
A Raz
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Unsaturated Fatty Acids ◽  
Human Platelet ◽  
Platelet Rich Plasma ◽  
Arachidonic Acid Metabolism ◽  
Ionophore A23187 ◽  
Low Concentrations ◽  
Induced Aggregation

SummaryThe role of arachidonic acid oxygenated products in human platelet aggregation induced by the ionophore A23187 was investigated. The ionophore produced an increased release of both saturated and unsaturated fatty acids and a concomitant increased formation of TxA2 and other arachidonate products. TxA2 (and possibly other cyclo oxygenase products) appears to have a significant role in ionophore-induced aggregation only when low concentrations (<1 μM) of the ionophore are employed.Testosterone added to rat or human platelet-rich plasma (PRP) was shown previously to potentiate platelet aggregation induced by ADP, adrenaline, collagen and arachidonic acid (1, 2). We show that testosterone also potentiates ionophore induced aggregation in washed platelets and in PRP. This potentiation was dose and time dependent and resulted from increased lipolysis and concomitant generation of TxA2 and other prostaglandin products. The testosterone potentiating effect was abolished by preincubation of the platelets with indomethacin.

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