REQUIREMENT OF NITRIC-OXIDE AND CALCIUM MOBILIZATION FOR THE INDUCTION OF APOPTOSIS IN ADRENAL VASCULAR ENDOTHELIAL-CELLS

Exposure of adrenal vascular endothelial cells (AVEC) to pharmacologic al nitric oxide (NO) donors, proinflammatory cytokines or lipopolysacc haride was unable to induce apoptosis as occurred when macrophages wer e treated under identical experimental conditions, However, when the i ntracellular Ca2+ concentration increased, AVEC displayed apoptotic fe atures upon exposure to NO, This apoptosis was confirmed by the releas e of oligonucleosomes to the cytosol and by the characteristic DNA lad dering observed after electrophoresis in agarose gels. Ca2+-mobilizing agents and interleukin-1 beta (IL-1 beta) also elicited an apoptotic response in these cells through a mechanism that required NO synthesis . The ability of NO and intracellular Ca2+ to promote apoptosis was de pendent on the number of passages of the cells in culture, suggesting the loss of protective factors in the course of ex vivo cell culture. Because AVEC exhibit an important capacity to increase the intracellul ar Ca2+ concentration in response to a wide array of agonists, this co ndition might affect the integrity of the vascular system under pathol ogical circumstances such as those prevailing in the course of septic shock. (C) 1997 Federation of European Biochemical Societies.