It is unknown if short-term and long-term intermittent hypobaric hypoxic challenges both exert
pro-apoptotic effects on Fas death receptor-dependent apoptotic pathway in rat hearts. Seventy-two
Sprague-Dawley rats were randomly assigned into two groups. First, short-term intermittent hypobaric
hypoxia (STIHH)-normobaric normoxia (n = 12), hypobaric hypoxia (380 mmHg, 12% O2, 8 hrs/day) for
1 day (n = 12), and for 4 days (n = 12) and second, long-term intermittent hypobaric hypoxia (LTIHH)-
normobaric normoxia (n = 12), hypobaric hypoxia for 1 week (n = 12) and 2 weeks (n = 12). After STIHH
or LTIHH challenge, Fas receptor related pathway and histopathological analysis in the excised left
ventricle was determined by Western blotting, RT-PCR, Hematoxylin-eosin staining, Masson trichrome
staining and TUNEL assay. Fas death receptor and TNFα were significantly decreased after STIHH
whereas Fas receptor, TNFα, FAS-associated death domain (FADD), and caspase 8 were increased after
LTIHH. In addition, cardiomyocyte disarray and fibrosis were observed in 1 week LTIHH. Cardiac
hypertrophy and more severe disarray, fibrosis and cardiac apoptotic activities were observed in 2 week
LTIHH. STIHH exerts anti-apoptotic effects on hearts such as downregulation of TNFα and Fas
receptor whereas LTIHH exerts pro-apoptotic effects such as upregulation of TNFα and Fas-mediated
apoptotic pathways and lead to cardiac fibrosis and apoptosis. Our findings imply that short-term
versus long-term intermittent hypobaric hypoxia exerted protective versus deleterious effects on hearts.
