15-hydroxy-11-alpha-9-alpha-(epoxymethano)prosta-5-13-dienoic-acid and Hemolysis

1. The role(s) of the endothelium in modulating the responsiveness of isolated circumflex coronary artery rings (o.d. = 2.0-2.5 mm and o.d. = 0.6-1.3 mm) from sheep was investigated under oxygenated and hypoxic conditions. 2. Removal of the endothelium abolished the contraction produced by lowering the PO2 from 620 to 8 mmHg (either under optimal resting tension or precontracted by 40 mM KCl). In denuded artery rings sudden hypoxia caused relaxation. 3. Under oxygenated conditions, removal of the endothelium augmented the vasoconstrictor effects of U46619, 5-hydroxytryptamine (5-HT) and K+. In the denuded artery rings, hypoxia abolished the contractile effects of U46619 and reduced the contractile effects of 5-HT and K+. 4. Under oxygenated conditions, the vasorelaxant effect of adenosine was depressed by removal of the endothelium. In endothelium-denuded preparations, the small relaxant effect of adenosine remaining was greatly potentiated. 5. Haemolysate (1 microliter ml-1) caused an endothelium-dependent contraction under oxygenated conditions. The hypoxic contraction observed in the artery ring under resting tension was significantly potentiated by haemolysate (1 microliter ml-1). Haemolysate 1 microliter ml-1 had no effect on the denuded artery rings under hypoxic conditions. 6. Haemolysate (1 microliter ml-1) potentiated the vasoconstrictor effects of U46619 (0.5 microM), 5-HT (1 microM) and K+ (24 mM) under oxygenated conditions. 7. These results indicate that endothelium profoundly modifies the effect of hypoxia on the responsiveness of sheep isolated left circumflex coronary artery rings.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Adenosine; Animals; Cats; Coronary Vessels; Endothelium, Vascular; Hemolysis; Hypoxia; In Vitro Techniques; Isometric Contraction; Muscle, Smooth, Vascular; Nitroprusside; Potassium; Prostaglandin Endoperoxides, Synthetic; Serotonin; Sheep; Substance P; Vasoconstrictor Agents

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