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elonging to spontaneous hlpertensive and dhal sensitive rats. It can be concluded that
the antiapoptotic protein Bcl-xl may play a significant role in the pathogenesis and
protection against heart failure, however the exact mechanisms supporting this protection
are still not known.
III.c.The role of oxidative stress in cardiac apoptosis
One of the most powerful stimuli for the induction of cellular death pathways
including apoptosis is oxidative stress (Webster et al. 1999; Zhao et al. 1999; Zhao et al.
2000). Although necrosis is thought to be the most prominent mode of cellular death in
myocytes exposed to oxidative stress, the low levels of oxidative stress that are below the
cytotoxic level, but are above the levels which activate hypertrophic signaling pathways,
will indefinitely cause apoptosis (Sawyer et aL.2002). It is also found that most sources
of oxidative stress are found to be potent pro-apoptotic agents (Arola et al. 2000; Cook et
al. 1999; Kotamraju et al. 2000). The exact mechanism through which oxidative stress
produces apoptosis is still not understood. However, it is considered that there is more
than one mechanism of oxidative stress-induced apoptosis and that these mechanisms are
highly dependent on the factors such as the origin of free radicals as well as the type of
free radicals produced. The development of apoptosis in cardiac myocytes exposed to
ischemia may also be caused by ischemia-induced lactate accumulation and consequent
development of acidosis in the cells (V/ebster et al. 1999). Von Harsdorf et al. (1999) has
shown that apoptosis induced by Oz may be significantly distinguished from apoptosis
induced by H2O2 administration (von Harsdorf et aL 1999). This study has reported that
the HzOz-induced apoptosis in cardiac myocytes was characterized by the activation of
the mitochondrial pathway of apoptosis, while the administration of Oz produced
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