sq-29548 and ozagrel

It has been shown that increases in intraluminal flow elicit dilation in venules, but the mediation of response is not yet clarified. We hypothesized that - in addition to nitric oxide (NO) and dilator prostaglandins (PGI(2)/ PGE(2)) - thromboxane A(2) (TxA(2)) contributes to the mediation of flow-induced responses of venules.. Isolated rat gracilis muscle venules (259 +/- 11 microm at 10 mm Hg) dilated as a function of intraluminal flow, which was augmented in the presence of the TxA(2) receptor antagonist SQ 29,548 or the TxA(2) synthase inhibitor ozagrel. In the presence of SQ 29,548, indomethacin or Nomega-nitro-L-arginine methyl-ester decreased flow-induced dilations, whereas in their simultaneous presence dilations were abolished. The selective cyclooxygenase (COX) 1 inhibitor SC 560 reduced, whereas the selective COX-2 inhibitor NS 398 enhanced flow-induced dilations. Immunohistochemistry showed that both COX-1 and COX-2 are present in the wall of venules.. In skeletal muscle venules, increases in intraluminal flow elicit production of constrictor TxA(2), in addition to the dilator NO and PGI(2)/PGE(2), with an overall effect of limited dilation. These mediators are likely to have important roles in the multiple feedback regulation of wall shear stress in venules during changes in blood flow velocity and/or viscosity.

Topics: Animals; Blood Flow Velocity; Blood Viscosity; Bridged Bicyclo Compounds, Heterocyclic; Cyclooxygenase 1; Cyclooxygenase 2; Dinoprostone; Enzyme Inhibitors; Epoprostenol; Fatty Acids, Unsaturated; Hydrazines; Male; Methacrylates; Muscle, Skeletal; NG-Nitroarginine Methyl Ester; Nitric Oxide; Prostaglandin H2; Rats; Rats, Wistar; Regional Blood Flow; Stress, Mechanical; Thromboxane A2; Venules

This study sought to determine whether in vivo inhibition of thromboxane A2 (TXA2) action contribute to attenuate hepatic damage after bile duct ligation (BDL). Male Wistar rats were assigned to sham operation or BDL. At the time of operation, infusion pump with saline, ozagrel natrium (TXA2 synthase inhibitor), or SQ29548 (TXA2 receptor antagonists) was implanted in the abdominal cavity. Plasma alanine aminotransferase, aspartate aminotransferase, hyaluronic acid, and total bilirubin levels were measured at 4 days after the operation. The levels of plasma TXB2, a stable metabolite of TXA2, were significantly increased after BDL. Gene expression of TXA2 synthase was also significantly upregulated in the liver. Nonetheless, either an inhibition of TXA2 synthesis by ozagrel natrium or a blockade of TXA2 receptor by SQ29548 has no effect in every measured parameter related to hepatic function. These results indicated that despite a highly increased production in the liver, TXA2 is not directly related to the hepatic injury in BDL rats.

Topics: Alanine Transaminase; Animals; Bilirubin; Bridged Bicyclo Compounds, Heterocyclic; Enzyme Inhibitors; Fatty Acids, Unsaturated; Gene Expression Regulation, Enzymologic; Hyaluronic Acid; Hydrazines; Liver; Liver Diseases; Male; Methacrylates; Rats; Rats, Wistar; Receptors, Thromboxane A2, Prostaglandin H2; Thromboxane A2; Thromboxane B2; Thromboxane-A Synthase; Time Factors

Stretch-induced contraction of rabbit pulmonary artery depends on endothelium-derived vasoactive prostanoids. We investigated which prostanoid(s) was responsible for the stretch-induced contraction of the artery, and whether integrin was involved in this mechanotransduction process. Stretch increased productions of untransformed prostaglandin H(2), prostaglandin E(2), prostaglandin F(2alpha), and thromboxane A(2) in the pulmonary artery with intact endothelium. A blocking peptide for integrins (RGD peptide) significantly inhibited productions of thromboxane A(2) and prostaglandin F(2alpha), but the peptide did not affect productions of untransformed prostaglandin H(2) and prostaglandin E(2), as well as contraction in response to stretch. SQ29,548, a prostaglandin H(2)/thromboxane A(2) receptor antagonist, inhibited the contractile response to not only stretch but also exogenous prostaglandin H(2). Acetylcholine (up to 30 microM) also contracted the artery in an endothelium-dependent manner. Ozagrel (10 nM-1 microM), an inhibitor of thromboxane synthase, abolished the production of thromboxane A(2), in response to both stretch and acetylcholine, whereas the inhibitor mostly inhibited acetylcholine-induced contraction, but it did not suppress stretch-induced contraction. The results suggested that prostaglandin H(2) and thromboxane A(2), either released from endothelium by mechanical stretch or by acetylcholine, produced contraction of rabbit pulmonary artery in a RGD-independent manner.

Topics: Acetylcholine; Animals; Bridged Bicyclo Compounds, Heterocyclic; Dinoprost; Dinoprostone; Endothelium, Vascular; Fatty Acids, Unsaturated; Hydrazines; In Vitro Techniques; Isometric Contraction; Methacrylates; Oligopeptides; Prostaglandin Antagonists; Prostaglandin H2; Pulmonary Artery; Rabbits; Receptors, Thromboxane A2, Prostaglandin H2; Stress, Mechanical; Thromboxane A2; Thromboxane-A Synthase; Vasoconstriction; Vasodilator Agents

Arachidonic acid (AA) is a potent inducer of platelet aggregation in vitro; this activity is due to its conversion to biologically active metabolites, prostaglandin (PG) endoperoxides and thromboxane A2 (TxA2). PG endoperoxides and TxA, are thought to act on the same receptor; however, at least two isoforms of this receptor have been identified. The aim of our work was to clarify whether endoperoxides and TxA2 activate the same or different receptor subtypes to induce aggregation and calcium movements in human platelets. AA-induced aggregation and calcium rises were still detectable in platelets preincubated with thromboxane synthase inhibitors, which suppress TxA2 formation and induce PGH2 accumulation, suggesting that PG endoperoxides can activate platelets. Exogenously added PGH2 was able to induce aggregation and calcium rises. Pretreatment of platelets with GR32191B or platelet activating factor, which desensitize one of the two receptor subtypes identified in platelets, did not prevent calcium rises induced by endogenously generated or by exogenouly added PGH2, indicating that TxA2 and PG endoperoxides share the same receptor subtype(s) to activate platelets. HEK-293 cells overexpressing either of the two thromboxane receptor isoforms cloned to date (TPalpha and TPbeta) and identified in human platelets, stimulated with PGH2, or with the stable endoperoxide analog U46619, formed inositol phosphates. These data show that endoperoxides and TXA2 mediate their effects on platelets acting on both, and the same, receptor isoform(s).

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Aspirin; Biphenyl Compounds; Blood Platelets; Bridged Bicyclo Compounds, Heterocyclic; Calcium Signaling; Cells, Cultured; Enzyme Inhibitors; Fatty Acids, Unsaturated; Heptanoic Acids; Humans; Hydrazines; Imidazoles; Inositol Phosphates; Kidney; Methacrylates; Phenylacetates; Platelet Activating Factor; Platelet Activation; Prostaglandin H2; Prostaglandins H; Protein Isoforms; Receptors, Thromboxane; Recombinant Fusion Proteins; Sulfonamides; Thromboxane A2; Thromboxane B2; Thromboxane-A Synthase

We evaluated the capacity of anti-aggregating agents to influence thromboxane A(2) and prostacyclin formation, arachidonic acid-endoperoxide redirection, platelet aggregation and vessel tone, in isolated rabbit aorta incubated with homologous platelets. Picotamide (N,N'bis(3-pyridinylmethyl)-4-methoxy-isophthalamide), the only dual thromboxane A(2)-synthase inhibitor/receptor antagonist in clinical use, inhibited arachidonic acid-induced platelet aggregation with low potency, increased 180-fold by aorta presence. It inhibited thromboxane A(2) formation in platelets and, in aorta presence, increased prostacyclin formation. Ozagrel (OKY-046, (E)-3-(4-(1-imidazolylmethyl)phenyl)-2-propenoic acid), a pure thromboxane A(2)-synthase inhibitor, behaved similarly to picotamide, although the aorta caused a higher (600-fold) shift. The potency of the antagonist SQ 29,548 (1S-(1 alpha,2 beta(5Z),3 beta,4 alpha))-7-(3((2-((phenylamino)carbonyl)hydrazino)methyl)-7-oxabicyclo(2.2.1)hept-2-yl)-5-heptenoic acid) was unaffected by aorta. In coincubation experiments, arachidonic acid-challenge increased thromboxane A(2)-dependent vessel tone; picotamide increased prostacyclin and reduced thromboxane A(2) formation and vasoconstriction. Ozagrel mimicked picotamide; aspirin (acetylsalicylic acid) reduced aorta contractility, thromboxane A(2) and prostacyclin formation. SQ 29,548 reduced vasoconstriction without affecting eicosanoids. We demonstrate the importance of redirection of eicosanoids in the mechanism of action of thromboxane A(2) inhibitors/antagonists within platelet-vascular wall interactions. These findings bear relevance in the development of novel anti-thrombotic drugs.

Topics: Animals; Aorta, Thoracic; Arachidonic Acid; Aspirin; Blood Platelets; Bridged Bicyclo Compounds, Heterocyclic; Cell Communication; Dinoprost; Endothelium, Vascular; Fatty Acids, Unsaturated; Hydrazines; In Vitro Techniques; Male; Methacrylates; Muscle Tonus; Muscle, Smooth, Vascular; Phthalic Acids; Platelet Activation; Platelet Aggregation Inhibitors; Rabbits; Receptors, Thromboxane; Thromboxane A2; Thromboxane-A Synthase

To clarify whether endothelium-derived contracting factor (EDCF) is developed in renal artery of hypertensive Dahl rats and whether prolonged oral L-arginine treatments prevent development of EDCF and hypertension.. The effect of prolonged salt treatment with or without L-arginine on the renal artery was examined.. Dahl salt-sensitive and -resistant rats were fed a 0.4 or an 8% NaCl diet for 4 weeks. High sodium intake increased arterial pressure in Dahl salt-sensitive rats. The rings of renal arteries were suspended for isometric tension recording. Only in the hypertensive rats, more than 1 micromol/l acetylcholine induced an endothelium-dependent contraction response. The contraction was completely inhibited by indomethacin or ONO-3708 [prostaglandin H2 (PGH2)/thromboxane A2 (TXA2) receptor antagonist], and partially inhibited by OKY-046 (TXA2 synthetase inhibitor). Acetylcholine-induced relaxation was significantly depressed in hypertensive rats, which was partially improved by SQ29548 (PGH2/TXA2 receptor antagonist). Oral L-arginine, but not ONO-8809 (orally active PGH2/TXA2 receptor antagonist) treatment, inhibited the contraction and amended the relaxation. The endothelium-independent contraction to TXA2 receptor agonist U46619 and relaxation to nitroprusside were not altered by L-arginine treatment The L-Arginine treatment reduced blood pressure and sodium retention with increases in urinary NO2-/NO3- and cGMP excretion. Hydralazine treatment also inhibited development of EDCF.. The present results suggest that impaired endothelium-dependent relaxation to acetylcholine is caused in part by induction of EDCF synthesis/release in renal arteries of hypertensive Dahl rats. L-arginine can attenuate sodium retention and development of hypertension, which lead to a decrease in EDCF synthesis in renal arteries.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Acetylcholine; Animals; Arginine; Blood Pressure; Bridged Bicyclo Compounds, Heterocyclic; Cyclic GMP; Endothelins; Endothelium, Vascular; Fatty Acids, Unsaturated; Hydralazine; Hydrazines; Hypertension; In Vitro Techniques; Indomethacin; Male; Methacrylates; Natriuresis; Nitrates; Nitrites; Nitroprusside; Rats; Rats, Inbred Dahl; Renal Artery; Thromboxane A2; Vasoconstriction

Ischemic injury is characterized by neutrophil (PMN)--endothelial cell adhesion and diapedesis associated with thromboxane (TX) generation. Neutrophil-endothelial cell interaction is regulated in part by the leukocyte adhesion receptor CD 18 glycoprotein complex and the endothelial intercellular adhesion molecule-1 (ICAM-1). This study tests the role of TX in ischemia-induced diapedesis and evaluates whether the diapedesis is regulated by neutrophil or endothelial adhesion receptors. Plasma derived from rabbit hind limbs made ischemic for 3 hours (n = 6) and reperfused for 10 minutes had increased levels of TXB2 3,450 pg/ml, which was higher than sham rabbit (n = 6) values of 653 pg/ml (p less than 0.05). When introduced into abraded skin chambers placed on the dorsum of other normal rabbits (n = 6), this ischemic plasma induced 1,000 pg/ml of new TX synthesis and diapedesis of 1,235 PMN/mm3. The total TX concentration and PMN accumulations in blister fluid were correlated (r = 0.88, p less than 0.05). In contrast, sham rabbit plasma induced no TX synthesis and diapedesis of only 77 PMN/mm3 (p less than 0.05). Administration of 50 ng/ml of authentic TXB2 into blisters induced an accumulation of 453 PMN/mm3, which was higher than that in saline controls (18 PMN/mm3) (p less than 0.05). Pretreatment of normal rabbits used for the diapedesis assay (n = 4) with the TX synthetase inhibitor OKY 046 (2 mg/kg/hr) limited ischemic plasma and authentic TXB2 induced diapedesis to 142 and 76 PMN/mm3, respectively (both p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Bridged Bicyclo Compounds, Heterocyclic; Capillaries; CD18 Antigens; Cell Adhesion Molecules; Dactinomycin; Endothelium, Vascular; Fatty Acids, Unsaturated; Hydrazines; Intercellular Adhesion Molecule-1; Ischemia; Male; Methacrylates; Muscles; Neutrophils; Rabbits; Receptors, Leukocyte-Adhesion; Reference Values; Regional Blood Flow; Reperfusion; Skin; Thromboxane B2; Thromboxane-A Synthase; Thromboxanes

The influence of eicosanoids on the proliferation of hepatoma (HTC) cells was studied in culture and in tumor-bearing rats. The cells in culture demonstrated a capacity to metabolize arachidonic acid to eicosanoids including thomboxane B2 and the prostaglandins E2 and F2 alpha a. An effect of these eicosanoids on cell proliferation was suggested by the decreased cell division seen with an inhibitor of cyclooxygenase, flurbiprofen. A biphasic effect on the proliferation of HTC cells was observed with increasing concentrations of prostaglandin F2 alpha. These studies were extended to tumor-bearing rats where inhibitory effects on the early stages of tumor growth were seen with flurbiprofen. Bleeding times were decreased in tumor-bearing rats but were restored to control values by treatment with flurbiprofen and an inhibitor of thromboxane synthetase, OKY 046. These drugs and a thromboxane/endoperoxide receptor antagonist, SQ 29, 548, were not observed to have statistically significant effects on isotope-labeled water distribution but they had substantial effects on the maintenance of body weight by tumor-bearing rats. The data suggested that the cachexia of tumor-bearing animals may be mediated at least in part by the action of eicosanoids.

Topics: Acrylates; Animals; Arachidonic Acid; Arachidonic Acids; Bridged Bicyclo Compounds, Heterocyclic; Cell Division; Chromatography, Thin Layer; Cyclooxygenase Inhibitors; Dinoprost; Dinoprostone; Eicosanoids; Fatty Acids, Unsaturated; Flurbiprofen; Hydrazines; Liver Neoplasms, Experimental; Male; Methacrylates; Rats; Thromboxane B2; Thromboxane-A Synthase; Tumor Cells, Cultured

The effect of cyclooxygenase inhibition in phorbol myristate acetate (PMA)-induced acute lung injury was studied in isolated constant-flow blood-perfused rabbit lungs. PMA caused a 51% increase in pulmonary arterial pressure (localized in the arterial and middle segments as measured by vascular occlusion pressures), a 71% increase in microvascular permeability (measured by the microvascular fluid filtration coefficient, Kf), and a nearly threefold increase in perfusate thromboxane (Tx) B2 levels. Cyclooxygenase inhibition with three chemically dissimilar inhibitors, indomethacin (10(-7) and 10(-6) M), meclofenamate (10(-6) M), and ibuprofen (10(-5) M), prevented the Kf increase without affecting the pulmonary arterial pressure increase or resistance distribution changes after PMA administration. The specific role of TxA2 was investigated by pretreatment with OKY-046, a specific Tx synthase inhibitor, or infusion of SQ 29548, a TxA2 receptor antagonist; both compounds failed to protect against either the PMA-induced permeability or the vascular resistance increase. These results indicate that cyclooxygenase-mediated products of arachidonic acid other than TxA2 mediate the PMA-induced permeability increase but not the hypertension.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Blood Pressure; Body Fluids; Bridged Bicyclo Compounds, Heterocyclic; Capillary Permeability; Cyclooxygenase Inhibitors; Fatty Acids, Unsaturated; Hydrazines; In Vitro Techniques; Male; Methacrylates; Prostaglandins; Pulmonary Circulation; Rabbits; Tetradecanoylphorbol Acetate; Thromboxane A2; Thromboxane-A Synthase; Vascular Resistance

Indirect evidence exists that the reperfusion of ischemic tissue activates white blood cells. Thus local and systemic reperfusion injuries are prevented by making animals leukopenic or by inhibiting white blood cell lung entrapment by blocking thromboxane A2 generation. This study tests directly whether ischemia and reperfusion activates neutrophils, as measured by their oxidative burst, and whether thromboxane mediates this event. Anesthetized rats underwent 4 hours of bilateral hind limb tourniquet ischemia followed by 60 minutes of reperfusion. Plasma thromboxane B2 levels increased to 2750 pg/ml at 5 minutes of reperfusion, higher than the sham control (n = 36) value of 370 pg/ml (p less than 0.01). In untreated ischemic animals (n = 30) the intracellular H2O2 production of circulating neutrophils, as assayed flow cytometrically by dichlorofluorescein oxidation, increased from a preischemic value of 133 to a peak of 251 femtomoles dichlorofluorescein/neutrophil at 5 minutes of reperfusion (p less than 0.01). Treatment of neutrophils with phorbol myristate acetate (PMA) 10(-7) mol/L led to a 91% increase in neutrophil H2O2 production before ischemia, and 5 minutes after reperfusion there was an enhanced response to PMA of 222% (p less than 0.01). Pretreatment of animals with the thromboxane-synthetase inhibitor OKY 046 (n = 36) prevented ischemia-induced thromboxane generation, neutrophil H2O2 production (p less than 0.05), as well as the enhanced response to PMA stimulation (p less than 0.05). Treatment with the thromboxane-receptor antagonist SQ 29,548 (n = 36) did not affect the increase in plasma thromboxane levels after ischemia but was as effective as OKY 046 in preventing the ischemia-induced increase in neutrophil H2O2 production and the enhanced response to PMA stimulation. These data indicate that lower-torso ischemia leads to neutrophil activation, manifest by H2O2 production, an event mediated by thromboxane.

Topics: Animals; Bridged Bicyclo Compounds, Heterocyclic; Fatty Acids, Unsaturated; Flow Cytometry; Hindlimb; Hydrazines; Hydrogen Peroxide; Ischemia; Male; Methacrylates; Neutrophils; Oxidation-Reduction; Rats; Rats, Inbred Strains; Receptors, Prostaglandin; Receptors, Thromboxane; Reperfusion; Thromboxane B2; Thromboxane-A Synthase; Thromboxanes

Lower torso ischemia and reperfusion lead to respiratory dysfunction characterized by pulmonary hypertension and increased lung microvascular permeability. This is associated with lung leukosequestration and thromboxane (TX) generation. This study tests the role of elevated TX levels following muscle ischemia in mediating remote lung injury. Anesthetized sheep prepared with chronic lung lymph fistulae underwent 2 hours of bilateral hind limb tourniquet ischemia. In untreated controls (n = 7), 1 minute after reperfusion there was a transient increase in plasma immunoreactive (i)-TXB2 levels from 211 to 735 pg/ml (p less than 0.05), and at 30 minutes, lung lymph i-TXB2 levels rose from 400 to 1,005 pg/ml (p less than 0.05). At 1 minute, the mean pulmonary arterial pressure (MPAP) increased from 13 to 38 mm Hg (p less than 0.05) and pulmonary microvascular pressure (Pmv) from 7 to 18 mm Hg (p less than 0.05). Lung lymph flow (QL) rose from 4.3 to 8.3 ml/30 min (p less than 0.05), the lymph/plasma (L/P) protein ratio was unchanged from 0.6, and the lymph protein clearance increased from 2.6 to 4.6 ml/30 min (p less than 0.05). Two hours after reperfusion, neutrophils were observed sequestered in lung capillaries and proteinaceous exudates were found in alveoli in contrast to sham-operated animals (n = 3). To maximize lung vascular surface area and achieve a pressure independent L/P protein ratio a left atrial balloon was inflated during one group of ischemia-reperfusion experiments (n = 5). This resulted in a baseline rise in MPAP to 20 mm Hg (p less than 0.05); a 4.3-fold increase in QL (p less than 0.05), a decrease in the L/P ratio from 0.70 to 0.28 (p less than 0.05) and a protein reflection coefficient (sigma d) of 0.72. During reperfusion the L/P ratio rose to 0.49 (p less than 0.05) and the sigma d decreased to 0.51 (p less than 0.05), documenting an increase in lung microvascular permeability. In contrast to untreated ischemic controls, inhibition of TX synthetase with OKY 046 (n = 6) reduced plasma i-TXB2 levels to 85 pg/ml (p less than 0.05) but also increased i-6-keto-PGF1 alpha levels to 78 pg/ml relative to 15 pg/ml in untreated controls (p less than 0.05). OKY 046 prevented the increase in MPAP, Pmv, QL, and lymph protein clearance (p less than 0.05). Lung histology was normal in distinction to the leukosequestration in untreated ischemic controls.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Animals; Blood Pressure; Bridged Bicyclo Compounds, Heterocyclic; Capillary Permeability; Drug Combinations; Fatty Acids, Unsaturated; Female; Hydrazines; Ibuprofen; Ischemia; Leg; Lung; Methacrylates; Microcirculation; Pulmonary Artery; Reperfusion; Sheep; Thromboxane A2; Thromboxane-A Synthase

We identified SPA in three young apparently healthy women. SPA was associated with release of TXA2 and was only partially inhibited by ADP-inhibitor apyrase and alpha 2-adrenoceptor blocker yohimbine. In vitro incubation of aspirin (90 micrograms/ml) or selective TXA2 synthetase inhibitor OKY-046 (0.1 uM) with platelet rich plasma (PRP) did not abolish SPA, although platelet generation of TXA2 was markedly inhibited. In contrast, oral administration of large amounts of aspirin in one subject or in vitro incubation of PRP with TXA2 -endoperoxide receptor blocker SQ 29,548 (20-100 nM) significantly inhibited SPA. These studies suggest that SPA is associated with TXA2 release. Since TXA2 -endoperoxide receptor blocker completely abolishes the secondary wave, agents like this may be of therapeutic value in individuals with SPA and evidence of tissue ischemia.

Topics: Adult; Apyrase; Aspirin; Blood Platelet Disorders; Blood Platelets; Bridged Bicyclo Compounds, Heterocyclic; Fatty Acids, Unsaturated; Female; Humans; Hydrazines; In Vitro Techniques; Methacrylates; Platelet Aggregation; Thromboxane A2; Yohimbine

There is evidence that tumors may stimulate platelet aggregation, causing release of thromboxane A2. Thromboxane A2 may potentiate tumor metastasis by stimulating tumor cell growth and proliferation and by enhancing platelet-tumor cell aggregate formation. Despite potential significance of thromboxane A2 in tumor metastasis, agents which inhibit thromboxane A2 synthesis have not been uniformly effective in reducing tumor metastasis. We, therefore, evaluated the effects of a thromboxane A2 receptor antagonist SQ-29,548 compared to those of a thromboxane A2 synthetase inhibitor OKY-046 on osteogenic sarcoma-induced platelet aggregation and thromboxane A2 release. Osteogenic sarcoma cells added to platelet-rich plasma caused complete and irreversible platelet aggregation as well as thromboxane A2 release. Preincubation of platelet-rich plasma with SQ-29,548 (2 to 20 nM) decreased platelet aggregation induced by tumor cells, but it had no effect on thromboxane A2 release. In contrast, preincubation of platelet-rich plasma with OKY-046 (0.1 to 10 microM) had no effect on platelet aggregation despite a decrease in thromboxane A2 synthesis. These results suggest that thromboxane A2 receptor blockers, rather than synthetase inhibitors, may prevent tumor cell-induced platelet aggregation.

Topics: Blood Platelets; Bridged Bicyclo Compounds, Heterocyclic; Cells, Cultured; Fatty Acids, Unsaturated; Humans; Hydrazines; Methacrylates; Osteosarcoma; Platelet Aggregation; Thromboxane A2