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

Abstract

1 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. 2 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. 3 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. 4 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. 5 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. 6 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. 7 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.