Stimulation of endothelial prostacyclin production plays no role in endothelium‐dependent relaxation of the pig aorta

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Abstract
Stimulation of prostacyclin production by pig aortic endothelial cells adhering to microcarrier beads supervised in columns, or 3H release from cells prelabelled with [3H]‐arachidonate, was studied in response to a range of agents that induce endothelium‐dependent vascular relaxation. Bradykinin, adenosine triphosphate (ATP) and ionophore A23187 each stimulated release of prostacyclin from unlabelled cells and of 3H from prelabelled cells but acetylcholine did not. Bradykinin induced a parallel, dose‐dependent increase in 3H release and 86Rb efflux, measured simultaneously from columns of aortic endothelial cells preloaded with 86Rb and [3H]‐arachidonate. The rank‐order of effectiveness at inducing both 3H and 86Rb release, measured simultaneously from columns of aortic endothelial cells prelabelled with 86Rb and [3H]‐arachidonate and challenged with maximal doses of each agonist, was: A23187 > bradykinin > ATP. The similarity between agonist‐induced 3H release (from cells prelabelled with [3H]‐arachidonate) and 86Rb efflux indicates that a common mechanism may be responsible, and the effectiveness of ionophore A23187 suggests that a rise in the intracellular level of calcium may be involved. The lack of effect of acetylcholine on release of prostacyclin from unlabelled cells or of 3H from cells prelabelled with [3H]‐arachidonate provides further evidence that acetylcholine acts on endothelial cells by a mechanism that does not involve calcium mobilisation. Although bradykinin, ATP and ionophore A23187 each induced release of prostacyclin from aortic endothelial cells, prostacyclin did not relax the pig aorta. Furthermore, endothelium‐dependent relaxation was unaffected by pretreating aortic strips with aspirin. It therefore appears that neither prostacyclin nor any other cyclo‐oxygenase product mediates endothelium‐dependent relaxation of the pig aorta.