A major contributor to the development and progression of ischemia-reperfusion (IR)-induced acute renal failure (ARF) is the loss of functioning tubular epithelial cells by means of various cell deletion or death processes. Although the term "acute tubular necrosis" is still used to describe the pathology of ARF, this is a misnomer because apoptotic cell death, as well as necrosis, occurs [1, 2] along with desquamation and loss of viable epithelial cells [3]. Apoptosis was first described in renal disease in 1987 in an animal model of hydronephrosis [4]. In ARF, with reference to only the death processes, the relative contribution of necrosis or apoptosis possibly depends on the extent of the initiating events. For example, after prolonged total renal ischemia, necrosis or "accidental cell death" occurs from the resultant negation of the cell's energy and protein levels. In apoptosis, the cells use their own energy processes and proteins to die, and often the initiating ischemia is more mild [5]. Finally, despite prolonged ischemia, within the heterogeneous renal cell populations there are those that are more sensitive to ischemia, such as the proximal straight tubule and to some extent the thick ascending limb (TAL) of the loop of Henle. It may be hypothesized that these cells tend to undergo necrosis in comparison with the less sensitive segments that undergo apoptosis. Because apoptosis is gene driven, its identification is important because of the possibility of its modulation via molecular controls. However, despite these new concepts of ARF, patient death remains high, at approximately 30 to 50% of ARF cases. Recovery from ARF depends not only on the replacement or regeneration of cells deleted by death, the theme of many recent studies, but also on protection of cells from death. Both processes are dependent on many of the cellular and molecular controls that have evolved in multicellular organisms to manage normal development, differentiation and growth processes, but that then become involved in the pathogenesis and progression of many renal diseases, including ARF.

Apoptosis was investigated by electron and light microscopy in the anterior pituitary gland of the male Fischer rat in which hyperplasia of prolactin-secreting cells had been induced by estrogen implanted subcutaneously for 6 weeks. Counts by light microscopy of apoptotic cells and cells containing phagocytosed apoptotic bodies increased during a period of 44 h after estrogen withdrawal. Necrosis was present but was not prominent. Administration of bromocriptine after estrogen withdrawal increased apoptotic counts to nearly double those in the absence of bromocriptine. Bromocriptine caused some increase in necrosis. Apoptosis occurred in prolactin-secreting cells identified by immunostaining and in other cells. Phagocytosed apoptotic bodies were seen in folliculo-stellate and not in other cells. It is concluded that apoptosis occurs in the anterior pituitary gland and is induced by bromocriptine. Phagocytosis of apoptotic bodies is a function of the folliculo-stellate cells.