Hypoxia- and endothelium-mediated changes in the pharmacological responsiveness of circumflex coronary artery rings from the sheep.

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.