thromboxane-a2 and Hemolysis

The two thromboxane A2 mimetics, carbocyclic thromboxane A2 (CTA2) and U-46619 (9,11-methanoepoxy PGH2) at concentrations of 400 ng/ml significantly enhanced the release of hemoglobin from both feline and human erythrocyte suspensions. This effect was significantly attenuated by the thromboxane receptor antagonist BM-13,505 indicating that the membrane leakiness is in some way receptor mediated. The effects also appear to be concentration-dependent over the range of 100-400 ng/ml. The membrane labilizing effect of thromboxane analogs is not due to a non-specific eicosanoid effect since iloprost, the stable prostacyclin analog, actually stabilized erythrocyte membranes. Moreover, synthetic thromboxane A2 exerted similar effects to that of the two TxA2-mimetics. This membrane labilizing action of thromboxanes may be important in propagating the other pathophysiologic effects of thromboxane A2 in cardiovascular disease states.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Animals; Cats; Hemoglobins; Hemolysis; Humans; In Vitro Techniques; Prostaglandin Endoperoxides, Synthetic; Thromboxane A2

The fast intravenous injection of arachidonic acid (AA) in mice produces, in a dose-related way, mortality due to respiratory distress. Upon electron microscopical examination an extensive oedematous damage of the capillary endothelium was found; thrombotic platelet obstructions were present in a minority of pulmonary capillaries only. Protection against this toxic AA-effect is obtained with inhibitors of fatty acid cyclo-oxygenase and of thromboxane (TXA2) synthetase, suggesting involvement of TXA2 as a causative mediator. The Ca2+-entry blockers flunarizine, niludipine and nimodipine, not affecting TXA2 synthesis by murine platelets, also provide protection, but not the antiplatelet drugs ticlopidine, dipyridamole or suloctidil; thrombocytopenia induced by busulphan does not affect the AA-induced mortality nor the protection obtained with flunarizine. Platelet-independent bronchoconstriction induced by AA in guinea-pigs is also inhibited by flunarizine. This study suggests that the AA-induced mortality test reflects pulmonary conversion of AA to TXA2 producing endothelial cell damage and respiratory smooth muscle cell contraction rather than a thrombotic phenomenon. The protective effect of flunarizine against TXA2 induced changes in vivo may contribute to its effectiveness in particular hypoxic conditions associated with liberation of AA.

Topics: Animals; Arachidonic Acid; Arachidonic Acids; Blood Platelets; Bronchi; Calcium Channel Blockers; Cinnarizine; Cyclooxygenase Inhibitors; Endothelium; Flunarizine; Guinea Pigs; Hemolysis; Male; Malondialdehyde; Mice; Muscle Contraction; Muscle, Smooth; Muscle, Smooth, Vascular; Piperazines; Receptors, Leukotriene; Receptors, Prostaglandin; Risk; Thromboxane A2; Thromboxane-A Synthase; Thromboxanes; Time Factors

Topics: Animals; Arachidonic Acids; Blood Proteins; Blood Transfusion, Autologous; Epoprostenol; Hemolysis; Heparin; Hypotension; Prostaglandins; Protamines; Protein Binding; Rabbits; Thromboxane A2; Thromboxanes