抄録
The purpose of this study was to elucidate whether the elevation of plasma lipoperoxide would suppress aortic prostacyclin production in vivo.
A new concept for the role of prostaglandins in the platelet function and arterial smooth muscle has established from the works of Samuelsson and Vane. In the platelet, arachidonic acid (AA) is generated to an unstable subtsance, thromboxane A2 which contracts arterial smooth muscle and causes platelet aggregation. On the other hand, in the arterial wall, AA is converted to an unstable substance, Prostacyclin (PG I2) which relaxes arterial wall and prevents platelet aggregation. Moncada and co-workers have reported that 15-hydroperoxy-AA, one of lipoperoxides, inhibits the production of PG I2 from aortic endothelial microsomes. It is well known that vitamin E prevents the elevation of lipoperoxide level in the plasma and tissues. Vitamin E deficient rats were used to investigate a correlation between the plasma lipoperoxide concentration and the aortic PG I2 production.
Three groups of male rats were observed, the first was fed with control meal for two months, the second with vit. E rich meal and the last with vit. E deficient meal. Plasma vit. E level was measured by the fluorometry and plasma lipoperoxide concentration was determined by the fluorometric method of Yagi. Plastelet aggregation induced by 2μM of ADP was studied with aggregometer. PG I2-like substance produced by the aorta was measured according to the method of Okuma. The aortic ring was incubated in borate-buffered saline (0.1M borate buffer, pH 9.0/0.154M NaCl=1:9, v/v) for one hour at 20°C. The amount of PG I2-like substance released into the buffer from the aorta was estimated by its anti-aggregatory effect on ADP-induced human platelet aggregation, and calculated per dry weight of the aorta.
The results are summarized as follows. The plasma vit. E levels of the E-rich group were higher than those of the control group, and those of the E-deficient group were lower than the control. The platelet aggregation rates did not reveal a significant difference between any groups. The plasma lipoperoxide concentrations of the E-deficient group (4.8±1.1n mol/ml, M±SD) were significantly higher than those of the control group (3.2±0.6) or the E-rich group (2.7±0.3), (p<0.05 p<0.01, respectively). On the other hand, the amount of PG I2-like substance produced by the aortae of the E-deficient group (5.3±2.7ng/mg. hr, M±SD) were significantly less than those of the control group (14.4±6.9) or the E-rich group (15.7±1.2), (P<0.05, P<0.001, respectively). Concerning the plasma lipoperoxide concentration or the PG I2-like substance, we could not find a significant difference between the Erich and control groups.
It is concluded that an abundance of lipoperoxide in the plasma suppresses the production of the PG I2 from the aortic wall, and this result coincides with the in vitro experiment by Moncada. In the patients with arteriosclerosis, diabetes mellitus or chronic pancreatitis, plasma lipoperoxide levels are elevated. We hypothesize that the aortic PG I2 would be suppressed in these diseases and it would be one of the causes or the progressive factors for vascular damages of them.
