The effect of angiotensin on cerebral blood vessel was studied in unanesthetized fourty-one rabbits comparing with the effect of noradrenaline on it. Both internal carotid blood flow and external carotid blood flow were measured with two photoelectric drop-recorders simultaneously. Angiotensin of 0.1 μg injected into the Internal carotid artery caused marked decrease in the blood flow through this artery and then the same amount of angiotensin injected into the external carotid artery also caused the similar degree of decrease in the blood flow through the external carotid artery. On the other hand, noradrenaline of 5 μg injected into the internal carotid artery caused a minimal decrease or an actual increase in the blood flow through this artery, whereas the same amount of noradrena-line injected into the external carotid artery caused a marked decrease in the external carotid blood flow. Consequently angiotensin is considered to have a specific vesoconstrictive effect on the cerebral blood vessel, which is different from noradrenaline.

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A male rat with spontaneously high systolic blood pressures of 150 to 175 mmHg persisting for more than one month and a female rat with blood pressures slighty above the average, 130 to 140 mmHg, were selected from among 68 Wistar strain rats in normal condition and mated to obtain F₁ rats. Of these F₁ rats, males and females with hypertension (blood pressure exceeding 150 mmHg) persisting for more than a month (mostly over 2 months) were mated to produce F₂ rats. The procedure was repeated to obtain F₃, F₄, F₅ and F₆ rats totaliag 380 animals. The weights and blood pressures (by the tail-water-plethysmographic method) were measured once weekly biginning at 4 weeks of age, and the results can be summarized as follows : 1. In body weight, the F rats showed little difference from the normal controls. 2. The blood pressures of F rats rose with age and from generation to generation, increasing significantly above those of normotensive controls of the same age after 20 weeks of age among female F₁, after 15 weeks among male F₁ and also male and female F₂, and after 10 weeks among all F₃ to F₆ rats. E. g., the average systolic blood pressure of F₅ at 25 weeks of age was 206+__-18.5 mmHg in the male and 193+__-20.5 mmHg in female rats. The blood pressures of normotensive controls remained at 131 to 136 mmHg in the male and 130 to 135 mmHg in female rats after 10 weeks of age. 3. Many F rats showed spontaneous hypertension. The incidence of the spontaneous occurrence of hypertension increased, and the development of hypertension occurred at younger ages from generation to generation. All of the F₃ to F₆, rats developed spontaneous hypertension within 15 weeks of age. Severe hypertension with blood pressures exceeding 200 mmHg began to observed among F₂. The incidence of such severe hypertension increased with each generation, so that among male animals it inceased from only 9% in F₂ to 35% in F₃, 42% in F₄, and 56% in F₅, and in female animals from 3% in F₂, 16% in F₃, 33% in F₄, and 37% in F₅. The authors have named this Wistar strain of rats with spontaneous occurrence of hypertension as "spontaneously hypertensive rats (Okamoto-Aoki)". 4. The blood pressures of β-line rats from parents with very high blood pressures were significantly higher than among α-line rats from parents with moderately high blood pressures at the same age. 5. There was no difference in the blood pressures of offsprings resulting from inbreeding and those from cross breeding. The male blood pressure averaged about 10.6 mmHg above the female value in spontaneous hypertension, and hypertension developed at lower ages in the male. 6. It is a question for future study whether the spontaneous hypertension induced in rats in this Study is comparable in characteristics with essential hypertension in man.

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Lots of problems remain unsettled as to the developmental mechanism of atherosclerosis despite efforts of many excellent researchers. Various sorts of factors, such as endocrine, dietary, genetic and acquired habitual, are supposed to take parts resulting in the abnormal metabolism of lipids, formation of thrombus, abnormal discharge of angiospastic substance, changes in blood pressure as well as structural alteration of the vascular wall. No satisfactory physiopathological studies have been carried out on the developmental mechanism of atherosclerosis. Attention has been payed to the relationship between stress and the development of atherosclerosis develops. Seifter and his colleagues demonstrated the formation of lipid mobilizer, a substance to increase serun lipids, in the serum of animals given cortisone or exposed to cold. The author has attempted to clarify the relatioship between stress and the developmental mechanism of atherosclerosis with special attention to the lipid mobilizer (LM). The present paper is to report the effects of LM on the development of atherosclerosis in the rabbits fed on lanolin. Material and Methods 1) Adult mal rabbits of the same age, ranging from 2.5 to 3.5 Kg in body weight, were used for the experiment. 2) Purification of lipid mobilizer. Intramuscular injection of cortisone acetate, 5 mg per kilogram, was performed on the adult rabbits that had been kept without feeding for 24 hours ; 7 hours later, the whole blood, being added with 10% sodium citrate, was obtained. The serum was separated and dialysed for 48 hours in running water, and then dialysed for 48 hours in Aq dest. The supernate was concentrated under slightly decreased pressure at 68°C, and then dried by freezing for the stock. The stock material was dissolved in physiological saline solution every time for use. 3) The rabbits were divided into 4 groups. Group 1 (control group) : Fed on pellet diet (RC 5), 200 g per day, and injected with physiological saline solution. Group 2 : Fed on the mixture of lanolin (20 g) and pellet diet (200 g), and injected with physiological saline solution. Group 3 : Fed on pellet diet, 200 g per day and injected with LM 5 mg per kilogram of body weight, every day.

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The author reported in the preceding paper (Studies on Atherosclerosis : Part 1) that the combined administration of lanolin and lipid mobilizer induces marked lipemia as well as atherosclerosis in the rabbits. Studies on lipid mobilizer (LM) in man have been reported by clinical findings with the quantitative changes of LM. The author attempted to measure the amount of LM in the human blood serum and to clearify its part in the development of atherosclerosis. Material and Methods 1) In vitro measurement of LM. LM was obtained and purified after Seifter's method from 2ml of the blood serum obtained from the hungry patients in the early morning. The amount of serum LM was evaluated according to its character to inhibit the activity of lipoprotein lipase. 0.3ml of lipoprotein lipase solution was added with 0.3ml of 10% human albumin solution (pH 8.5), 0.3ml of lipid mobilizer solution and 4.0ml of diluted cow's milk (1 in 600, dilutant : 0.25M NH₃-NH₄Cl, pH 3.5 diluted three times with saline), and incubated at 37°C for two hours. After the procedure the turbidity was compared. 2) Purification of lipoprotein lipase. Periepididymal and perirenal adipose tissue of male rats were put in the cold acetone (O°C, 30 times as much as the tissue), and homogenized at O°C, and then centrifuged in 6000 rpm for 20 minutes. The supernate was discarded. The precipitate was repeatedly washed in cold acetone and ether, and then dried under the decreased pressure in low temperature. This stock powder was dissolved in 0.025M NH₃NH₄Cl buffer solution (pH 8.6) at O°C and left for 60 minutes, and centrifuged in 8000 rpm for 30 minutes, and then the supernate was diluted in a proper way every time for use. 3) Preparation of anti-β-lipoprotein. Human blood serum containing a large amount of β-lipoprotein was added with 20 times as much volume of 4mg/dl dextran sulfate in physiological saline solution containing sodium citrate. 15-60 minutes later, this mixture was centrifuged in 6000 rpm for 30 minutes. The supernate was discarded. The same procedure was repeated 5 or 6 times to get the pure β-lipoprotein. 15-20 mg dose of this preparation was injected in to the rabbit subcutaneously 15 times. After the procedure, anti-β-lipoprotein-seurm was obtained. This serum reacted specifically with β-lipoprotein to form a single precipitation zone in agar gel double diffusion method (after Ouchterlony). 4) Patients with coronary disease, hypertension and cerebrovascular disease were subjected to this experiment. Healthy adult persons were examined as the control.

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