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Biomedical subjects

V C Menys

Publications and source records attributed to V C Menys.

26 records · Page 2Linked to original sources
PubMed1984

Thromboxane-mediated activation of platelets and enhancement of platelet uptake onto collagen-coated glass or deendothelialized rabbit aorta. Comparative effects of a thromboxane antagonist (EPO45) and a thromboxane synthetase inhibitor (dazoxiben).

The effects of a cyclooxygenase inhibitor (indomethacin), a thromboxane synthetase inhibitor (dazoxiben), and a thromboxane antagonist (EPO45) on rabbit platelet aggregation induced by collagen were studied and compared with effects on platelet uptake both by damaged rabbit aorta and by collagen-coated glass. Platelet aggregation and associated release of serotonin were inhibited to a similar extent both by indomethacin and EPO45. Dazoxiben had a minimal inhibitory effect on aggregation but reduced the release of serotonin by about 40% compared with control. Platelet uptake onto collagen-coated glass was markedly reduced both by indomethacin and EPO45 but not by dazoxiben. In contrast, EPO45 and dazoxiben were equally effective in reducing platelet adhesion to damaged rabbit aorta. At the concentrations used for adhesion studies the formation of thromboxane B2 was reduced both by dazoxiben and by indomethacin (both greater than 95% inhibition compared with control) and to a lesser extent by EPO45 (less than 40% inhibition). The results indicate that thromboxane A2 (and cyclic endoperoxide) released by adherent platelets may enhance thromboxane synthesis and promote platelet uptake both onto collagen-coated glass and onto damaged rabbit aorta. In the presence of vascular tissue, cyclic endoperoxides are readily metabolized and thereby removed. The potential antithrombotic activity of TXA2 synthetase inhibitors could be impaired in situations in which endoperoxide clearance is limited (e.g., accompanying platelet uptake onto artificial surfaces) but not at the damaged vessel wall. Thus, both inhibitors and antagonists are likely to have similar potency as antithrombotic agents in vivo.

6-Ketoprostaglandin F1 alpha↗
PubMed1983

Selective inhibition of thromboxane synthetase with dazoxiben - basis of its inhibitory effect on platelet adhesion.

Platelet adhesion to rabbit aortic subendothelium or collagen-coated glass was quantitated in a rotating probe device by uptake of radio-labelled platelets. Under conditions in which aspirin had no effect, dazoxiben, a selective inhibitor of thromboxane synthetase, reduced platelet adhesion to aortic subendothelium by about 40% but did not affect adhesion to collagen-coated glass. Pre-treatment of aortic segments with 15-HPETE, a selective inhibitor of PGI2-synthetase, abolished the inhibitory effect of dazoxiben on adhesion. Concentrations of 6-oxo-PGF1 alpha in the perfusate were raised in the presence of dazoxiben alone, and following addition of thrombin (10 units/ml) there was a 2--3 fold increase in concentration. Perfusion of damaged aorta with platelets labelled with (14C)-arachidonic acid in the presence of thrombin and dazoxiben resulted in the appearance of (14C)-labelled-6-oxo-PGF1 alpha. Inhibition of thromboxane synthetase limits platelet adhesion probably by promoting vascular synthesis of PGI2 from endoperoxides liberated from adherent platelets, which subsequently promotes detachment of cells from the surface.

6-Ketoprostaglandin F1 alpha↗
PubMed1983

Inhibitory effects of ZK 36374, a stable prostacyclin analogue, on adhesion of rabbit platelets to damaged aorta and serotonin release by adherent platelets.

The effects of ZK 36374, a prostacyclin analogue, were studied on adhesion of rabbit platelets to damaged rabbit aorta and on activation of platelets (judged by release of serotonin and formation of thromboxane-B2) in response to the processes of adhesion to the vessel surface and aggregation in response to microfibrillar collagen in suspension. In the presence of ZK 36374 (10-100 nmol/l), platelet adhesion and thromboxane-B2 formation were progressively reduced. The extent of serotonin release from adherent platelets was similar to that found for platelets aggregated with collagen. However, higher concentrations of ZK 36374 were required to inhibit serotonin release from adherent platelets than from aggregated platelets. The results indicate that ZK 36374 acts similarly to native prostacyclin on adhesion and collagen-induced aggregation and unlike previously described analogues is equipotent. The mechanism of release of serotonin induced by adhesion of platelets is less sensitive to the action of ZK 36374 than that of release induced by aggregation in response to microfibrillar collagen in suspension.

6-Ketoprostaglandin F1 alpha↗
PubMed1983

Effect of dazoxiben on platelet-vessel wall interaction.

1 Platelet monolayer adhesion to damaged rabbit aorta and to collagen-coated glass was quantified in a perfusion device. Addition of the thromboxane synthetase inhibitor dazoxiben (UK 37248) 1 and 10 microM reduced adhesion to damaged blood vessel by about 45% at both concentrations, but did not affect adhesion to collagen-coated glass. 2 Measurement by RIA indicated virtual abolition of thromboxane B2 production in the presence of the drug and a slight trend to an increase of 6-oxo-prostaglandin F1 alpha concentration in experiments using aorta. Inhibitory activity of dazoxiben was abolished by previous exposure of the aorta to 15-HPETE(?), an inhibitor of prostacyclin synthetase. 3 The results indicate that dazoxiben inhibits platelet adhesion to vascular subendothelium possibly by promoting synthesis of PGI2 from re-directed platelet endoperoxides.

Animals↗
PubMed1982

Effect of heparin on platelet monolayer adhesion, aggregation and production of malondialdehyde.

Heparin inhibited monolayer adhesion of washed human and rabbit platelets to collagen-coated glass at 2.5 and 20 units/ml concentration, in the absence of red cells. Adhesion of rabbit platelets to de-endothelialized rabbit aorta, under similar conditions, was less strongly inhibited but no inhibition was seen at 40% haematocrit. Addition of plasma reduced, rather than enhanced heparin activity and hirudin 0.5 units/ml had no significant effect. Heparin also inhibited platelet aggregation, release of (14C) 5-HT and production of malondialdehyde in response to collagen and thrombin. Inhibition of thrombin-induced activity was greater in the presence of plasma. However, heparin enhanced aggregation and release evoked by ADP and did not consistently inhibit MDA synthesis produced by arachidonate. The results indicate that in addition to the effects of heparin on platelet function mediated by anti-thrombin activity and the previously described augmentation of responses to ADP, heparin has weak inhibitory activity against platelet-collagen interactions. Binding of heparin to the platelet membrane (and to surfaces to which platelets adhere) could account for these findings by causing non-specific interference with agonist-receptor interactions.

Adenosine Diphosphate↗
PubMed1982

Aspirin, prostacyclin and post-occlusive reactive hyperaemia in man.

We studied post-occlusive reactive hyperaemia using ecg-triggered mercury strain-gauge plethysmography in eight normal subjects treated with incremental doses of aspirin (27.5-1200 mg). The reactive hyperaemic response was measured in the finger (predominantly skin blood flow) and the calf (predominantly muscle). Concentrations of TXB2 and 6-oxo-PGF1 alpha were measured in venous effluent blood from the hand by RIA, following arterial occlusion. Levels of TXB2 were significantly higher at 0-10 and 60-70 seconds (p less than 0.01), and 90-100 seconds (p less than 0.05) following release of occlusion compared to pre-occlusion values. However there was no significant change in concentrations of 6-oxo-PGF1 alpha and therefore by this method release of prostacyclin during reactive hyperaemia in the hand. Aspirin had no influence on finger or calf reactive hyperaemia 90 minutes after dosing, despite marked inhibition of platelet MDA production (75% after 110 mg, maximal inhibition after 1200 mg). These data provide no support for the hypothesis that prostacyclin is involved in the determination of the post-occlusive reactive hyperaemic response in the finger and calf in man.

6-Ketoprostaglandin F1 alpha↗