Na + /K + pump and endothelial cell survival: [Na + ] i /[K + ] i -independent necrosis triggered by ouabain, and protection against apoptosis mediated by elevation of [Na + ] i

摘要: Recent studies have demonstrated the tissue-specific effect of Na+/K+ pump inhibition by ouabain and other cardiac glycosides on cell viability. The vascular endothelium is an initial target employed for management congestive heart failure as well circulating endogenous ouabain-like substances (EOLS), production which augmented in volume-expanded hypertension. This study examined role survival cultured porcine aortic endothelial cells (PAEC). Complete with led to PAEC death, indicated detachment decreased staining 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). Based swelling resistance benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (z-VAD.fmk) a pan-caspase inhibitor, this type death was classified necrosis. In contrast ouabain, K+-free medium did not affect viability sharply attenuated apoptosis triggered 3H decay-induced DNA damage. Necrosis evoked preserved after dissipation transmembrane gradient K+ Na+, whereas Na+ abolished antiapoptotic action medium. Comparative analysis these results modulation intracellular content above-listed stimuli showed that interaction Na+/K+-ATPase necrosis independently pump-mediated ion fluxes inversion [Na+]i/[K+]i ratio, protection against under K+-depleted mediated [Na+]i elevation. regulation remodelling seen hypertension should be investigated further context EOLS chronic treatment digitalis.