In order to investigate metabolism of HDL, following experiments have been made in this study.
1) Chylomicron which obtained from high fat fed dog was injected intravenousely to the hepatectomized and control dogs. And, 0.1mg/Kg of heparin also intravenousely injected to the subjects. Then, production of HDL from chylomicron was investigated.
2) To obtain the information on the direction of metabolism of HDL subfraction (HDL₂ and HDL₃), LCAT activities of various lipoproteins were determined by the method of Glomuset and Akanuma in vitro.
3) Nicomol (1200mg/day), Niceritrol (750mg/day), Cholestyramin (12g/day), Cs-500 (HMG CO-A reductase inhibitor, 15-30mg/day), MDS (dextran sulfate, 1800mg/day) and probucol (1000-1500mg/day) were administerd to the hyperlipidemic patients for 4 weeks. And, effects of the drugs on serum lipids, lipoproteins and lipoprotein lipids were studied.
Determination methods: Cholesterol and phospholipid by enzymatic method. Triglyceride by acetyl-aceton method. Separation and determination of lipoproteins by ultracentrifugation.
Results:
1) In the hepatectomized dogs, HDL₃ increased significantly within 10 minutes after the heparin injection and decresaed gradually and returned to preheparin level around 50 minutes after the administration. HDL₂ and LDL did not change at all. In the control dogs, HDL₃ increased significantly around 10 minutes after the heparin injection and decreased gradually and returned preheparin level around 50 minutes after the injection. In this cases, HDL₂ and LDL also increased slightly within 15 minutes after the injection.
2) LCAT activities of Various Lipoproteins were as follows; HDL₃ 24.8%, HDL₂ 5.5%, LDL 1.9% and VLDL 1.8%.
3) Marked decreases of VLDL and LDL were caused by the antilipemic agents administration. Serum cholesterol and triglyceride levels also decreased. Furthermore, Increases of HDL₂ and HDL₃ occured by the drug administrations except probucol. However, in the cases administered the probucol, β/α lipoprotein ratio decreased since decreases of LDL and VLDL were more greater than decrease of HDL.
Discussions and conclusions: The results obtained in this study indicate that catabolism of chylomicron produces the HDL₃ and LCAT activities mainly locates into HDL₃ indicating that HDL₃ may be a most important substrate of LCAT. These evidences strongly suggest that metabolism of HDL subfractions might progress from HDL₃ toward HDL₂ by the uptake of membrane cholesterol into HDL₃. Conversion of chylomicron to LDL and that of HDL₃ to HDL₂ seems to required the existance of HTGL or liver cell since these conversions were only observed in the nonhepatectomized dogs. Furthermore, data suggest that catabolism of HDL₃ may be made at some other tissues or organs than liver.
Many efforts has been spended in attempt to increase the HDL as an prevention of atherosclerosis. However, our results shows that easier way to increase the HDL is to decrease the LDL and VLDL since, in such occasion, HDL increases automatically.

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Atherosclerotic changes in 417 consecutive autopsy cases over one year old during two years from January 1977 to December 1978 were macroscopically examined. Atherosclerotic index (A. I.) was calculated in 410 aortas, 396 coronary arteries, and 222 cerebral arteries. Relation between A. I. and sex, serum cholesterol, blood pressure was also investigated.
1. A. I. of aortas showed higher index in patients over 40 years of age. No sex predilection was found. Positive relation between A. I. of aorta and blood pressure was present in hypercholesteremic patients of 50-69 years of age.
2. A. I. of coronary arteries showed higher index in male patients over 40 years of age, and in female over 60 years of age. No sex predilection was found. Positive relation between A. I. of coronary arteries and serum cholesterol or blood pressure was not present.
3. A. I. of cerebral arteries showed higher index in patients over 60 years of age. No sex predilection was found. Positive relation between A. I. of cerebral arteries and blood pressure was present in the patients over 70 years of age.

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To define the etiologic factors of cerebral infarcttion and myocardial infarction in Japan, epidemiological and pathological studies were carried out. The results are summarized as follows:
1) In the groups with the traditional Japanese life styles as Akita inhabitants, cerebral and myocardial infarction are mainly caused by atherosclerosis which is not induced by hyperlipidemia. It is hypertension that is a main risk factor for atherosclerosis.
2) In the groups with the most westernized life styles in Japan such as executives in big cities, cerebral and coronary ischemic lesions are caused by atherosclerosis with hyperlipidemia.
3) Then, it seems that there is different pathogenesis of these diseases among the populations with different life styles.
4) The recent increase of cerebral infarction and myocardial infarction does not only result from the increase of hyperlipidemia derived from the westernization of living environment in Japan, but also the increase of atherosclerosis which is induced mainly by hypertension. We consider that the increase of atherosclerosis without hyperlipidemia is due to the prolongation of period of hypertension which derived from the decrease of cerebral hemorrhage in younger age.

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In the majority of patients with ischemic heart disease, atherosclerotic change of major coronary artery were thought to be its causative disease. However, since the development of selective coronary angiographic technique, some observers have recently pointed to the existence of myocardial ischemia without atherosclerotic change in coronary angiogram. Some of these patients have normal coronary artery and others have non-atheromatous changes in coronary arteries.
Study of the underlying causative disease of the myocardial ischemia is very important to discuss the treatment and prognosis of the patients. To evaluate the underlying causative disease of myocardial ischemia, clinical data and selective coronary angiogram were analysed.
1) Non-atherosclerotic coronary heart disease (Table 2, 3 & 4)
In our clinic, a significant non-atheromatous stenosis of coronary artery was often seen in aortitis syndrome. Myocardial infarction and angina pectoris due to this syndrome were found in ten patients, two of the former and eight of the latter. An autopsied case of 24 year-old young man had a sudden death due to a proliferative ostial stenosis of left main coronary artery (Table 2). In various disease, three patients of myocardial infarction and eleven of angina pectoris were found including congenital coronary abnormalities (coronary aneurysm, rudimentary hypoplastic right coronary artery), MCLS and miscellaneous diseases (Table 4). It might be concluded that aortitis syndrome and rudimentary hypoplastic right coronary artery were a important underlying diseases of non-atherosclerotic coronary abnormalities.
2) Myocardial infarction and angina pectoris with the normal coronary artery (Table 5)
Two cases of acute myocardial infarction and eight angina pectoris associated with arteriographically normal coronary arteries were reported in this paper. Spasm of right coronary artery was suggested as etiology of acute myocardial infarction in two cases. In angina pectoris with ST elevation or depression during attack, coronary spasm without evidence of atherosclerotic coronary stenosis was demonstrated angiographically by the stress of exercise and medicament.
It was suggested that myocardial squeezing, angiographically functional obstruction during systole, which found in 55 pts. (9.1%), might be the cause of a ischemic heart disease and a conduction disturbance.

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In 120 patients with myocardial infarction (MI), we studied (1) the incidence of patients with normal cholesterol (T.C.) level, (2) HDL cholesterol (HDL-C) level in these patients and (3) correlation between T. C. and coronary arteriosclerosis on the one hand and HDL-C and coronary arteriosclerosis on the other.
The cases in which T. C. levels on the day of onset of MI were not more than 220mg/dl numbered 59 (67%) out of 88 patients.
More than two months after the onset of the disease the T. C. level generally rose, but 32 patients (36.4%) did not show high T. C. level (220mg/dl or more).
As to the fluctuations in the T. C. level after the onset of the disease, minimum level was shown within one week in 6 (20%) and within one week to one month in 8 (27%), while the T. C. level remained unchanged or rose in 16 (53%) out of 30 cases of which T. C. on the day of onset was not more than 220mg/dl.
In the cases of which T. C. level was not less than 220mg/dl, meanwhile, the greater part of cases (9 out of 17 cases) showed minimum level within one week to one month and the rate of the T. C. falling off was also conspicuous compared with the cases of which T. C. level was not more than 220mg/dl.
With males, the T. C. level for those aged under 60 years was 243.2±73.6mg/dl and that for those above 60 years of age was 185.5±48.9mg/dl, the former showing a significantly high level (p<0.01).
As for the HDL-C level, there was no significant difference between the two groups, but the HDL-C/T. C ratio was high (p<0.05) in the group of patients aged above 60 years (18.8±6.6%) contrary to the result of the T.C level.
With males, a significant negative correlation was observed between the T. C level and the HDL-C/T.C ratio (r=-0.643, p<0.01).
Regarding the correlation between the T.C. level and the number of coronary arteries involved, the lower the T.C level, the more the case of one vessel disease, and as the T.C level rose, the case of 2 vessel or 3 vessel disease increased in number.
As to the correlation between the HDL-C and the number of coronary arteries involved, the more the HDL-C level rose, the less became the number of coronary arteries involved, but there were some exceptional cases, and the negative correlation was not as close as that observed between the HDL-C/T.C ratio and the number of coronary arteries involved.
There was no correlation between triglyceride and the number of coronary arteries involved.

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Sex-age-obesity-blood pressure adjusted frequency of ECG abnormality (I-1-2, I-3, IV-1-3, V-1-4 by Minnesota Code) was compared in terms of the type of GTT in the total of 5001 cases. The cases with known diabetes and hyperlipidemia were not included in the above subjects. The adjusted frequency of I-3, IV-1-3, and V-1-4 was not different among normal, borderline and diabetic groups of GTT. The frequency was much strongly influenced by blood pressure, sex and age than the GTT abnormality.
On the other hand, the adjusted frequency of I-1-2 tended to become higher with GTT abnormality. It has been reported, however, that insulin plays more important role in the pathogenesis of arteriosclerosis than serum glucose value. The cases with abnormal GTT excluding known diabetes may have higher insulin level than the cases with normal GTT. Further more, there would be many diabetics in cases with diabetic type even though known diabetics had been excluded, and possible effects of the abnormal blood coagulality and fibrinolytic activity, and microangiopathy upon IHD must be taken into consideration. The question whether the abnormal glucose metabolism itself promotes the arteriosclerosis or not hardly be answered as a conclusion of this study.

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Importance of hyperlipoproteinemia to the development of atherosclerosis has been well established already. However, there exist many patients with atherosclerotic disease such as ischemic heart disease and cerebral infarction with hypolipidemia. Generally, in such patients, the atherosclerosis has been progressed without so called risk factors. In concerning with atherogenesis of such patients with hypolipidemia, role of lipid metabolism might be still important. Purpose of this study is to investigate the lipid metabolism and effect of Vitamin E to the lipid metabolism in the hypolipidemic atherosclerotic patients.
Method: 33 cases of male patient with atherosclerotic disease and 30 cases of healthy matched control have been subjected. The subjects were subdivided into two groups, first with hyperlipidemia and second hypolipidemia. Then, serum lipids and lipoproteins levels, and plasma fatty acid compositions were determined. 300mg/daily of α-tocopherol were administered to the 11 cases of hypolipidemic patient for 12 weeks. Furthermore 3 of 11 cases were administered the medication for 4 weeks after the 6 weeks of discontinuation. Then, serum lipids, lipoproteins and various lipoprotein α-tocopherol were investigated.
Results: 1) In the hyperlipidemic patients, percentage of plasma linoleic acid were significantly reduced as compaired with that of controls. Contraversely, percentage of plasma linoleic acid of hypolipidemic patients were significantly higher than that of controls.
2) In the hyperlipidemic patients, serum HDL levels and distribution of V.E to HDL decreased as compaired with those of the controls. However, V.E content of 1000mg of HDL were not so much different between both groups. In the hypolipidemic patients, serum HDL levels and V.E distribution to HDL also decreased. Furthermore, V.E content of 1000mg of HDL decreased significantly.
3) Administration of V.E did not affect to the V.E content of HDL at all in the hypolipidemic patients distinctly.
Discussion and conclusion: From the aspects of lipids, lipoproteins and fatty acid composition, hyper and hypo lipidemic patients belong to the different populations. And, it seems that lipoperoxide might play important role as one of the atherogenesis in the hypolipidemic patients since, percentage of linoleic acid in the lipoprotein lipids is high and HDL-V.E is low. Furthermore, it is difficult to increase the HDL-V.E by the administration of V.E orally.
Above mentioned evidences may indicate atherogenesis of lipoperoxide should be stressed especially in the hypolipidemic subjects.

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Precipitation methods for the assay of HDL-cholesterol were examined using four different reagents, such as heparin-Mn⁺⁺, heparin-Ca⁺⁺, dextran sulfate-Mg⁺⁺ and sodium phosphotungstate-Mg⁺⁺.
For the isolation of HDL by former three reagents, the assay system was consisted of 0.1ml of test serum and 2ml of the reagent was used. The mixture was allowed to stand for 30min. at 4°C before centrifugation at 1, 500 G for 15min. at 4°C. In sodium phosphotungstate-Mg⁺⁺, 0.5ml of test serum was added to 0.05ml of the reagent and the mixture was allowed to stand for 5min. at room temperature before centrifugation.
Cholesterol levels in the supernate were determined by enzymatic method.
On the basis of these analysis, the optimum condition for polyanion and cation in the precipitation reagents were instituted as follows:
Heparin-Mn⁺⁺ (48.10mg/dl, 0.0600M, NaCl: 0.125M) heparin-Ca⁺⁺ (47.62mg/dl, 0.0238M), dextran sulfate-Mg⁺⁺ (1.5%, 0.1125M) and sodium phosphotungstate-Mg⁺⁺ (0.4%, 0.0500M, pH 6.20).
We estimated the capability of four precipitation methods for the isolation of HDL. For this purpose, we used Ouchterlony double diffusion method.
The correlation coefficient between ultracentrifugation method (UC) and heparin-Mn⁺⁺ method was 0.882, that between UC and heparin-Ca⁺⁺ method was 0.972 and that between UC and sodium phosphotungstate-Mg⁺⁺ method was 0.889. In the case of dextran sulfate-Mg⁺⁺ method, the correlation coefficient between UC was 0.831-0.839, showing a difference when a reagent from different lot number was employed.
Thus, it is postulated that heparin-Ca⁺⁺ method for the assay of HDL in the routine work could be the best among various precipitation methods currently available.

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When high density lipoprotein (HDL) cholesterol concentration for healthy subject was simultaneously determined by both precipitation (heparin-Ca²⁺ or dextran-sulfate-Mg²⁺) and ultracentrifugation methods, these values were well correlated with each other. In survivors of cerebral infarction, however, a considerable discrepancy was sometimes observed between HDL-cholesterol concentrations determined by the two methods. We had found three male survivors of cerebral infarction having a large difference which was subsequently confirmed on reexamination. In these patients, it was shown that HDL₂:HDL₃ cholesterol ratio was higher than that in healthy control and that chemical composition of HDL₂ was characteristically different from that in healthy control; cholesterol content was higher and phospholipid content was lower than those of healthy control. These results suggest that such a discrepancy is due, not to inadequate precipitation conditions but rather to increased amount of abnormal lipoproteins which have a density of more than 1.063 and precipitate at the presence of polyanion and divalent cation. The most probable candidate lipoprotein may be Lp (a).

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The purpose of the present study was to compare the several current methods for quantitation of high density lipoprotein cholesterol (HDL-C). HDL was fractionated by ultracentrifugation or precipitation procedures utilizing heparin-MnCl₂ (heparin-Mn), reagents of which were prepared by ourselves, heparin-CaCl₂ (heparin-Ca; N company's kit), phosphotungustate-MgCl₂ (PT-Mg; F company's kit) or dextran sulfate-MgCl₂ (Dex-Mg; NK company's kit). Cholesterol concentrations in HDL separated by ultracentrifugation and by precipitation procedure using heparin-Mn Cl₂ were measured by o-phthalaldehyde (OPA) method. Cholesterol concentrations in HDL separated by other precipitation procedures were analyzed by enzymatic method utilizing the kit from N company. HDL-C (Mean±SD) measured by ultracentrifugation procedure, heparin-Mn procedure, heparin-Ca procedure, PT-Mg procedure and Dex-Mg procedure were 48.1±12.6, 45.6±11.0, 29.6±13.2, 24.1±11.5 and 24.4±11.2 mg/100ml, respectively. There was no significant difference between HDL-C value obtained by ultracentrifugation procedure and that by heparin-Mn procedure. However, HDL-C values obtained by other three precipitation procedures utilizing the kits were significantly lower than the value by ultracentrifugation procedure. Correlation coefficients among 5 methods were statistically significant. The data were analyzed separately in two groups; the first group in which HDL-C by ultracentrifugation procedure was equal to and higher than 40mg/100ml and the second group in which HDL-C was lower than 40mg/100ml. In both groups, mean values of HDL-C determined by three kits were significantly lower than that obtained by ultracentrifugation. In order to investigate the effects of cholesterol measurement on HDL-C values obtained by precipitation procedure, HDL-C of 22 patients were measured by heparin-Mn and heparin-Ca procedure. Cholesterol in supernatant after precipitation were analyzed by OPA method and enzymatic method utilizing N company's kit. HDL-C measured by heparin-Mn procedure with cholesterol measurement by OPA, heparin-Mn procedure with cholesterol measurement by enzymatic method, heparin-Mn procedure (W company's kit) and heparin-Ca procedure (N company's kit) with cholesterol measurement by enzymatic method were 44.7±9.5, 42.5±13.1, 30.3±12.2 and 28.1±10.9mg/100ml, respectively. There was no difference between the HDL-C values obtained by heparin-Mn procedure with cholesterol measurement by OPA and enzymatic method. The HDL-C values measured by heparin-Mn and heparin-Ca procedure (kit) with cholesterol measured by enzymatic method were significantly lower than HDL-C measured by heparin-Mn procedure with cholesterol measurement by OPA method. Therefore, we could not decide apparently different effects of OPA method and enzymatic method for cholesterol determination in HDL fractionated by different precipitation procedures. Factors which could affect HDL fractionation by precipitation procedure such as polyanion concentration, divalent cation concentration, pH of solution for precipitation, pH of solution after mixing plasma with precipitation solution and ratio of solution volume to plasma volume, were investigated. All these factors were within optimum range. However, the ratio of solution volume to plasma volume might be one of the problems. The presence of Apo A-I in the precipitates has been reported. We studied the occurrence of Apo A-I in the precipitates obtained by precipitation procedure utilizing anti-Apo A-I serum. There were precipitin lines observed between precipitates and anti-Apo A-I serum by double immunodiffusion method. The further studies are necessary to quantitate Apo A-I in the precipitates obtained by different precipitation procedures. Furthermore, sometimes, background staining or turbidity of reagent blank f

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A simple procedure is presented to separate serum high density lipoprotein (HDL) into the two subfractions (HDL₂ and HDL₃) by polyacrylamide gel electrophoresis (PAGE). A 6.75% polyacrylamide gel in 7cm long glass tube and the use of Tris/glycine buffer, pH 8.4, accomplished this separation. The serum lipoproteins were pre-stained with Sudan Black B and electrophoresed for about 90 min at 5mA per gel tube. After completion of electrophoresis, densitometry was performed directly on the tubes containing the gels at 600nm.
The β-lipoprotein was retained on the bottom of the stacking gel. The α-lipoprotein migrated into the separating gel, being separated into the two main components. The fast migrating component of α-lipoprotein was identified as HDL₃ and the slow one identified as HDL₂ by the electrophoresis of either HDL₃ or HDL₂ separated by sequential ultracentrifugation. The relative amounts of Sudan Black B stained HDL₂ and HDL₃ were obtained by integrating the densitometrically traced peak areas of the two components respectively. The HDL cholesterol (HDL-C) concentration of the serum was determined by precipitation (heparin-Ca²⁺) method. The concentration of serum HDL₂-C and HDL₃-C can be calculated from the results of these two methods; i. e., the densitometric analysis of polyacrylamide gel and the precipitation method.
The HDL₂-C and HDL₃-C concentrations measured by this PAGE and precipitation method were well correlated with the values obtained by the ultracentrifugation method. The correlation coefficients for HDL₂-C and HDL₃-C were 0.91 and 0.90, respectively. Thus, the combination of PAGE and precipitation method for HDL₂-C and HDL₃-C determination appears to be used as a rapid and reliable screening technique for clinical laboratories.
Both the HDL₂-C and HDL₃-C concentrations of survivors of cerebral infarction determined by the method described above were lower than those of healthy subjects, and these differences were larger in the HDL₂-C concentration than in the HDL₃-C one.

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Total cholesterol (TCH), triglyceride (TG), HDL-cholesterol (HDL-CH), LDL-cholesterol (LDL-CH) and atherogenic indices (AI₁=TCH-HDL-CH/HDL-CH, AI₂=LDL-CH/HDL-CH) were studied in 971 healthy Japanese male inhabitants of Tokyo, Kawasaki, Mizushima and Takaoka.
HDL-CH was significantly lower in Takaoka (49±11mg/dl) and in Mizushima (52±11mg/dl) than in Tokyo (58±13mg/dl) and in Kawasaki (58±14mg/dl). The area difference of HDL-CH was very similar to that of TG, but not to that of TCH.
Atherogenic indices were significantly higher in Takaoka (2.93±0.86, 2.44±0.75) and in Mizushima (2.84±0.79, 2.28±0.66) than in Tokyo (2.61±0.81, 2.00±0.69) and in Kawasaki (2.38±0.90, 1.75±0.81).
The prefectural mortality due to cardiac or cerebrovascular disease in 1978 was higher in the area with lower HDL-CH or with higher atherogenic indices. This suggested a clinical and epidemiological value of HDL-CH and atherogenic indices.

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Plasma lipids in cord blood drawn from 49 normal newborns were determined. Maternal plasma obtained shortly before the delivery were also analyzed. Sixty-two healthy adults (28 males and 34 females) aged 20 to 39 were adopted as control subjects.
Total cholesterol (TC), triglyceride, phospholipids, HDL-cholesterol (HDL-Ch), and HDL-phospholipids in cord blood were 72±20.3mg/dl, 69±16.0mg/dl, 134±37.0mg/dl, 39±11.6mg/dl, and 82±17.9mg/dl, respectively. All these values were significantly lower than the control values. HDL-Ch/TC ratio in cord blood was 0.57±0.16 and it was significantly larger as compared with control value (0.36±0.10). Cord blood HDL-Ch level in Japanese might be ranked relatively high among reported values in various countries. More prominent feature was that HDL-Ch/TC ratio was much larger than the values reported in western countries. Therefore, it can be said that, at least in neonatal period, Japanese has relatively smaller amount of LDL-cholesterol than western people.
Maternal administration of prostaglandin E₂ (PG) caused the difference in HDL-Ch concentration. Cord blood HDL-Ch in PG-treated group was significantly lower than that in non-treated group.
Percent ester cholesterol in HDL (HDL-CE) was evaluated measuring the free cholesterol content of HDL. The values in cord blood and maternal blood were 72±6.1% and 80±4.1%, respectively. HDL-CE in cord blood was significantly lower as compared with the control value (81±4.9%). Inverse relationship was observed between cord blood HDL-CE and birth weight. These results may indicate the possibility of low cholesterol-removing capacity of HDL in newborn infants. Our suggestion is that the rate of cholesterol-removal from peripheral tissues may be low in newborns actively utilizing cholesterol. The larger the birth weight is, the lower the rate might be.
Neonatal HDL-Ch and HDL-CE correlated directly with each corresponding value in maternal blood. Placental transfer of HDL as intact particles might occur as suggested before (Tamai et al., 1979).

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Although closed relationship between incidence of IHD and plasma level of HDL cholesterol has been reported recently, few epidemiological investigation based on field study was performed in our country.
We performed epidemiological survey and measurement of HDL choleserol utilizing heparinmangon method in a farming village of Takeno school area, Tanushimaru, Fukuoka. The subjects were consisted of 1, 003 male and females, aged 20 to 69 years. Plasma level of HDL cholesterol was contrasted with the presently known influencial factors of HDL cholesterol. Plasma HDL cholesterol level showed normal distribution at the peak value of 40-44mg/dl both female and male. Mean value was 47.02±11.74mg/dl for male and 49.51±11.26 for female showing significantly higher level in female. Although aging did not affect the value both in female and male, female had higher HDL cholesterol level than male in younger age group. Obesity lowered HDL cholesterol level both in female and male, which was also clearly demonstrated by ∑skin-fold.
Negative correlationship was found between serum TG and HDL cholesterol both female and male. The more the amount of cigarette smoking, the lower the value of HDL cholesterol. As to alcoholic intake (sake), highest value of HDL cholesterol was found in the group with daily alcoholic consumption of 180 to 360ml. Systolic blood pressure did not affect the value of HDL cholesterol.
It was concluded that the presently known influencial factors of HDL cholesterol seemed to affect similarly in our subjects as previously reported.
It was also interesting to note the close negative correlationship of HDL cholesterol and ∑skin-fold.

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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.

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Effects of trapidil (Rocornal^®) on the metabolism of cholesterol and lipoprotein in rats were studied. Trapidil increased serum high density lipoprotein cholesterol (HDL-cholesterol) level and decreased serum low density lipoprotein cholesterol (LDL-cholesterol) level and the ratio of HDL-cholesterol to LDL-cholesterol. On the basis of these data, a possible mechanism of action of trapidil was investigated. Uptakes of ¹⁴C-acetate into cholesterol in serum, liver and small intestine were suppressed with trapidil. Both blood and bile ¹⁴C-cholesterol were significantly decreased and the radioactivity excretion in bile was markedly increased with trapidil. Trapidil increased HDL-apoprotein, HDL-apoprotein A-I in serum and apoprotein A-I in lymph of small intestine. Moreover, half life of ¹²⁵I-HDL in plasma was significantly prolonged and that of ¹²⁵I-LDL was significantly shortened with trapidil. These date suggested that trapidil inhibits the cholesterol biosynthesis and stimulates the catabolism and excretion of cholesterol, and biosynthesis of HDL-apoprotein, especially apoprotein A-I.

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