The Effect of Endralazine and Hydralazine on Platelet Thromboxane Production in Vitro

1987 ◽  
Vol 6 (3) ◽  
pp. 375-386
Author(s):  
I. A. Greer ◽  
J. J. Walker ◽  
M. McLaren ◽  
A. A. Calder ◽  
C. D. Forbes
Keyword(s):  
Thromboxane Production ◽  
Platelet Thromboxane

Rapeseed Oil and Sunflower Oil Diets Enhance Platelet In Vitro Aggregation and Thromboxane Production in Healthy Men when Compared with Milk Fat or Habitual Diets

1992 ◽  
Vol 67 (03) ◽  
pp. 352-356 ◽  
Author(s):  
Marja Mutanen ◽  
Riitta Freese ◽  
Liisa M Valsta ◽  
Irma Ahola ◽  
Antti Ahlström
Keyword(s):  
Sunflower Oil ◽  
Milk Fat ◽  
Rapeseed Oil ◽  
Controlled Trial ◽  
Collagen Concentration ◽  
Aggregation Pattern ◽  
Thromboxane Production ◽  
Low Erucic Acid ◽  
Platelet Thromboxane

SummaryIn this highly controlled trial, 26 normolipidemic men (average age 28 years, range 18 to 60) were fed a baseline diet high in milk fat (MF) (fat 36% of energy, saturates 19%, monounsaturates 11%, polyunsaturates 4%), followed by a diet high in sunflower oil (SO) (fat 38% of energy, saturates 13%, monounsaturates 10%, polyunsaturates 13%) and another diet high in low erucic-acid rapeseed oil (RO) (fat 38% of energy, saturates 12%, monounsaturates 16%, polyunsaturates 8%). All diets were mixed natural diets with the same cholesterol contents. The baseline milk fat diet was given for 14 days and the oil diets for 24 days in a blind cross-over design. The platelet in vitro aggregation (slope %/min) induced by 1, 2 and 3 pM ADP and collagen (25 pg/ml PRP) was highly significantly (p <0.001) increased after both oil diets when compared with the results from the milk fat diet. The aggregation pattern determined by threshold collagen concentration confirmed increased collagen sensitivity of the platelets after the rapeseed oil diet (p <0.001). The enhancement of platelet aggregation was associated with increased in vitro platelet thromboxane production after the oil diets vs. the milk fat diet (p <0.05 after the sunflower oil diet and p <0.001 after the rapeseed oil diet).

NIACIN-INDUCED PROSTACYCLIN (PGI2) GENERATION AND THE SEARCH FOR THE IDEAL DOSE OF ASPIRIN

1987 ◽  
Author(s):  
J A Jakubowski ◽  
D Deykin
Keyword(s):  
Plasma Levels ◽  
Chronic Administration ◽  
Normal Subjects ◽  
Enteric Coated Aspirin ◽  
Regular Aspirin ◽  
Thromboxane Production ◽  
Enteric Coated ◽  
Platelet Thromboxane

We have previously reported that chronic administration of 80 mg/day of enteric-coated aspirin (ECA) in three divided doses of 27 mg each day for 7 days produced over 90% inhibition of platelet thromboxane production. What we wanted to know was whether that dose of aspirin spared PGI2 production. We developed a sensitive plasma assay for PGI2 (measured as 6-keto-PGF1a). We confirmed the reports of others that normal plasma levels are very low, less than 2 pg/ml. We selected niacin as a provocative challenge to raise plasma levels of PGI2 to test the ability of a given aspirin regimen to spare or suppress PGI2 production in vivo. In 5 normal subjects an oral dose of 3 mg/kg of niacin produced a 3-fold rise in 6-keto-PGF1a from 0.86 to 2.64 pg/ml. A dose of 5 mg/kg produced a rise to 6.6 pg/ml. Administration of 323 mg of regular aspirin/day for 7 days completely abolished niacin-induced elevation of plasma PGI2. The lowest dose of ECA that we have found effective in suppressing platelet thromboxane production in vitro, 80 mg/day in divided doses of 27 mg three times a day for 7 days, also completely suppressed niacin-induced elevation of PGI2. Our data do not support the hyypothesis that a very low dose of ECA selectively suppress platelet thromboxane production but spares generation of PGI2

In Vitro Effects Of 5-Fluorouracil On Vascular Tissue Prostacyclin Release And Platelet Thromboxane Production

1981 ◽  
Author(s):  
L Caprino ◽  
F Antonetti ◽  
M Lagomarsino ◽  
L Morelli
Keyword(s):  
Platelet Aggregation ◽  
Vascular Tissue ◽  
Wet Weight ◽  
Thromboxane Production ◽  
In Vitro Effects ◽  
Dose Levels ◽  
Dose Dependent Increase ◽  
Platelet Thromboxane

Severe chest pain (angina attacks) and myocardial infarction has been recorded during 5-Fluorouracil (5-F.U.) tre atment. The present study was undertaken to evaluate the "in vitro" activity of 5-F.U. on vascular prostacyclin (PGI ) release and platelet thromboxane A2(TXA2) formation, which play a role in the onset of cardiovascular disorders. Rat aortic rings (about 20 mg wet/weight) were incubated at 30*C for 15 mins in 300 pi tris buffer containing 5-F.U. (250-500-1000 yg). The aortic rings were removed and the supernatant was kept 4 hrs at room temperature and the RIA of 6-keto PGF1α was thereafter performed.In 1 ml rabbit PRP containing 5-F.U. (50-100-500 yg) platelet aggregation was induced by Arachidonic acid (45 μg). Platelets were then removed by centrifugation and RIA of TXB2 was performed on supernatant.At the dose levels of 250, 500, 1000 μg, 5-F.U. yielded a dose-dependent increase (20, 44 and 68 percent, respectively) in the 6-keto PGF2 released by rat aortic rings. Coil versely, the TXB2 production by platelets during aggregation was reduced of 19, 27, 36 percent at 5-F.U. concentrations of 50, 100, 500 μg/ml, respectively. 5-F.U. had no effect on platelet aggregation.Considering the vasodilator and antithrombogenic effects of PGI2 and the vasoconstrictor effect of TXA2 the present results are not in agreement with the already described cardiotoxicity of 5-F.U. The “in vitro” results, however, if confirmed “in vivo”, show a new aspect of the mechanism of 5-F.U. cardiotoxicity.

The Interrelationship between Thromboxane Biosynthesis, Aggregation and 5-Hydroxytryptamine Secretion in Human Platelets in Vitro

1980 ◽  
Vol 43 (01) ◽  
pp. 038-040 ◽  
Author(s):  
L C Best ◽  
T K Holland ◽  
P B B Jones ◽  
R G G Russell
Keyword(s):  
Human Platelet ◽  
Human Platelets ◽  
Dense Granule ◽  
Thromboxane B2 ◽  
Essential Requirement ◽  
Direct Mechanism ◽  
Thromboxane Synthetase ◽  
Thromboxane Production ◽  
Higher Doses

SummaryPlatelet aggregation, secretion of 5-hydroxy tryptamine and production of thromboxane B2 were monitored simultaneously in human platelet suspensions in the absence and presence of cyclooxygenase or thromboxane synthetase inhibitors. Aggregation, secretion and thromboxane B2 formation in response to either sodium arachidonate or epinephrine were blocked by aspirin or by 1-N-butyl imidazole suggesting that thromboxane biosynthesis was an essential requirement for platelet activation by these agents. In contrast, thrombin and collagen could apparently induce aggregation and secretion via two pathways: at low doses involving thromboxane production, but at higher doses by a direct mechanism independent of thromboxane biosynthesis. In the case of ADP, inhibition of thromboxane production blocked secretion but had little effect on aggregation, indicating that secretion was probably dependent on thromboxane biosynthesis which probably occurred as a result of aggregation. Thus it appears that although the processes of thromboxane production, release of dense granule constituents and aggregation may often be intimately linked, each process can occur independently of the other, depending upon the stimulus used.

Platelet thromboxane production during endotoxin shock

1981 ◽  
Vol 11 (6-7) ◽  
pp. 648-650 ◽  
Author(s):  
Arthur Prancan ◽  
David Simon ◽  
Larry Pope
Keyword(s):  
Endotoxin Shock ◽  
Thromboxane Production ◽  
Platelet Thromboxane

Dietary fatty acids and platelet thromboxane production in puerperal women and their offspring

1986 ◽  
Vol 155 (1) ◽  
pp. 146-149 ◽  
Author(s):  
Pekka Kääpä ◽  
Matti Uhari ◽  
Tapio Nikkari ◽  
Lasse Viinikka ◽  
Olavi Ylikorkala
Keyword(s):  
Fatty Acids ◽  
Dietary Fatty Acids ◽  
Thromboxane Production ◽  
Platelet Thromboxane

Lack Of Inhibition Of Thromboxane Production Despite Inhibition Of Platelet Function By 1,3-Bis(2 Chloroethyl)-1-Nitrosourea (BCNU)

1981 ◽  
Author(s):  
R McKenna ◽  
T Ahmad ◽  
A Prancan ◽  
D Simon ◽  
H Frischer
Keyword(s):  
Arachidonic Acid ◽  
Oxygen Consumption ◽  
Platelet Aggregation ◽  
Acetylsalicylic Acid ◽  
Platelet Function ◽  
Human Platelet ◽  
Thromboxane A2 ◽  
Rabbit Aorta ◽  
Thromboxane Production ◽  
Platelet Thromboxane

We have previously shown that BCNU inhibits human platelet glutathione reductase (GSSG-R) prior to inhibiting platelet function; since thromboxane production is important in platelet function, we evaluated the effect of BCNU induced inhibition of GSSG-R on platelet thromboxane production.Control platelet GSSG-R activity was 0.091 ]jmoles NAD(P)H oxidized min-1lmg-1 protein at 37°C (±0.015 S.D.; n=9); inhibition was detectable at 10-7M% BCNU (70% of control) with a >90% inhibition at and above 10-5M BCNU. Platelet aggregation in response to 1.5×10-3M Arachidonic acid (AA), 10 μM epinephrine, 6 μg/ml equine collagen and 3 μM ADP were inhibited at 10-5M BCNU and abolished at 10-4 BCNU.BCNU (10-3M) did not affect the increase in oxygen consumption induced by AA. Using the rabbit aorta superfusion bioassay for thromboxane A2 (TXA2), threshold concentrations of AA in 10-5 and 10-4 BCNU platelets resulted in an increased measure of aortic tension 13.5 ± 9.4 mm S.D. (n=6) and 23.2 ± 9.5 mm respectively, compared with control values of 4.5 ± 2.4. Acetylsalicylic acid (5 × l0-4M) inhibited the contraction: 1.7 ± 1.1 (n=5). The conversion of 14C AA to thromboxane B2 (TXB2) and PGE2, as measured by radio TLC, was not decreased in BCNU treated platelets. There is a significant increase in TXB2 (p<0.05;n=4) and in the ratio of TXB2:PGE2 in platelets treated with 10-4M BCNU and 10-3M imidazole when compared to platelets treated with imidazole alone.In conclusion BCNU induced inhibition of platelet GSSG-R and platelet function occurs despite preservation of thromboxane production

Effect of platelet depletion on lung vasoconstriction in heparin-protamine reactions

1989 ◽  
Vol 66 (5) ◽  
pp. 2344-2350 ◽  
Author(s):  
G. Montalescot ◽  
E. Kreil ◽  
K. Lynch ◽  
E. M. Greene ◽  
A. Torres ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Platelet Aggregation ◽  
Fold Increase ◽  
Bovine Thrombin ◽  
Thromboxane Production ◽  
Acute Pulmonary Hypertension ◽  
Arterial Plasma ◽  
Arterial Po2 ◽  
Platelet Depletion

In six awake sheep the control heparin-protamine reaction was associated with a 150-fold rise in arterial plasma thromboxane B2 (TxB2) levels, a 4.5-fold increase in pulmonary vascular resistance, a 20% decrease in cardiac output, a 30% decrease in arterial PO2, and a 30% reduction in arterial white blood cell concentrations. Depletion of 99% of circulating platelets by antibodies did not prevent either acute and severe pulmonary hypertension or increased plasma TxB2 levels induced by heparin-protamine administration. We produced sheep platelet aggregation in vitro with bovine thrombin and measured marked TxB2 release (36.3 +/- 16.3 ng/10(9) platelets). In contrast, neither heparin, protamine, nor heparin-protamine complexes over a 10,000-fold range of concentrations induced platelet aggregation and release of thromboxane in vitro. Therefore sheep platelets are not the source of thromboxane production associated with acute pulmonary hypertension during the heparin-protamine reaction, and other cells must produce the thromboxane.

scholarly journals Erythrocytes metabolically enhance collagen-induced platelet responsiveness via increased thromboxane production, adenosine diphosphate release, and recruitment

Blood ◽  
1991 ◽  
Vol 78 (1) ◽  
pp. 154-162 ◽  
Author(s):  
J Valles ◽  
MT Santos ◽  
J Aznar ◽  
AJ Marcus ◽  
V Martinez-Sales ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Therapeutic Potential ◽  
Platelet Reactivity ◽  
Adenosine Diphosphate ◽  
Stimulus Response ◽  
Absolute Requirement ◽  
Thromboxane Production ◽  
And Function ◽  
Aspirin Ingestion

Abstract Erythrocytes promoted platelet reactivity in a plasma medium, as demonstrated in an in vitro system that independently evaluated the biochemistry of platelet activation and recruitment. The prothrombotic erythrocyte effects were metabolically regulated, as evidenced by lack of activity of ATP-depleted or glutaraldehyde-fixed erythrocytes. They occurred in the absence of cell lysis as verified by lactate dehydrogenase assays, and had an absolute requirement for platelet activation. The presence of erythrocytes induced a twofold increase in platelet thromboxane B2 (TXB2) synthesis upon collagen stimulation, indicating that erythrocytes modulated platelet eicosanoid formation. Cell-free releasates from stimulated platelet-erythrocyte suspensions, which exhibited increased recruiting capacity, contained 6.9-fold more ADP and 4.9-fold more ATP than releasates from stimulated platelets alone. Following aspirin ingestion, TXB2 formation was blocked, but erythrocyte promotion of platelet reactivity persisted at those doses of collagen that reinduced platelet activation. Moreover, when platelet mixtures consisted of as little as 10% obtained before aspirin plus 90% obtained post-aspirin ingestion, significant erythrocyte enhancement of platelet reactivity occurred, even at low agonist concentrations. These erythrocyte effects would decrease the therapeutic potential of inhibition of platelet cyclooxygenase by aspirin. The erythrocyte- induced modulation of platelet biochemistry and function emphasizes the importance of cell-cell interactions in stimulus-response coupling.

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