1984 年 12 巻 5 号 p. 1073-1081
It has been reported that the systemic hypoxia aggravates the development of atherosclerotic lesion of the aorta and the systemic hyperoxia suppresses it, but the mechanisms are not known.
The aim of this study is to clarify the significance of oxygen inhalation. The experiments were dedesigned to observe the effect of hyperoxic (40%) or hypoxic (10%) oxygen inhalation on the development of atherosclerosis in rabbit with dietary induced hypercholesterolemia or with spontaneous hyperlipidemia from birth for 8 weeks, and to investigate the effects of hypoxia (2%) on the smooth muscle cell or fibroblast which were cultured in the MEM supplemented with 20 hyperlipemic serum or 20% normolipemic serum of rabbit.
Results obtained were as follows:
1) Atherosclerotic lesions depicted by % area were decreased in the hyperoxia group and increased in the hypoxia group, when these two groups were compared.
2) The levels in plasma lipoperoxide were increased by both of them, but the increments were much higher in hypoxic condition than in hyperoxic condition.
3) There were significant correlation between the % aortic lesions and the lipoperoxide contents in aorta.
4) The contents of hydroxyprolin in aorta (Precursor of collagen) were much higher in hypoxic group than hyperoxic group.
5) The esterified cholesterol contents in the cells under the hypoxic condition were raised 2-3 folds as much as those in control, when the cells were incubated in the medium supplemented with hyperlipemic serum.
6) Lipoperoxide contents in the cell were increased under the hypoxic condition and reversed by the addition of antioxidant, a-tocopherol, under the identical condition.
7) The generation of Prostacyclin in the rabbit's aorta was suppressed under the condition of hypoxia.
From these results, we speculated that under the hyperlipidemic condition, cell hypoxia played an important role in atherogenesis, resulting in the accumulation of esterified cholesterol and lipoperoxide, and the suppression of prostacyclin generation. The hypothetical schema about the atherogenesis from the view of hyperlipidemia was illustrated in Fig. 18.