Effects of changes in extra- and intracellular K+ on the endothelial production of prostacyclin.

1. Changes in the KCl concentration of the incubation medium, from 0 to 80 mM, had no effect on the basal or ATP-stimulated release of prostacyclin (PGI2) from bovine aortic endothelial cells. 2. The monovalent cation ionophores, valinomycin and nigericin (5 microM), enhanced the release of PGI2 from endothelial cells stimulated by ATP or bradykinin. 3. The action of nigericin, unlike that of valinomycin, was time-dependent, abolished in a high-KCl medium and associated with an increased efflux of 86Rb and a time-dependent depletion of intracellular K+. 4. Ouabain (1-100 microM) also enhanced the release of PGI2 in response to ATP and induced a significant depletion of intracellular K+ in bovine aortic endothelial cells. 5. In conclusion, modifications of the endothelial cell membrane potential, resulting from changes in the extracellular K+ concentration, do not modulate the basal or ATP-stimulated production of PGI2. An acute depletion of intracellular K+ by nigericin or ouabain enhances the production of PGI2 in aortic endothelial cells stimulated by ATP or bradykinin.