There have been a lot of studies on the correlation between hypertension and vascular lesions.
Since Winternitz and Asscher produced vascular lesions by administering kidney homogenate in dogs and rats, many kinds of experiments were attempted to separate the vasotoxic factor from the pressor substance.
In Japan too, there have been made various studies, some reported that the cause of vascular lesions in experimental hypertension is vascular permeability substance existing in the kidney and some others showed the vascular changes in the experimental animals administered with non-pressor substance of the renal cortical extracts.
The vascular necrotizing fraction was obtained by ultracentrifugation of norml rat kidney, which contained non-pressor substance in our present experiment.
Characteristic lesions 24 hours after administration of vascular necrotizing fraction of the renal extracts to bilateral nephrectomized rats were necrosis of the small arteries.
In electron microscopic observation, early vascular damage occured in medial smoth muscle cells and sometimes with serous permeation in subendothelial matrices.
Another experiment of ours was to produce the vascular lesions by freezing the renal cortex in vivo.
Vascular changes of the mesentery and intestinal tract observed in this experimental rats were similar to those lesions produced by renal cortical extracts.
By two our experments, we confirmed that the renal cortex contains necrotizing substance for vascular walls.
It seems very important to investigate the necrotizing substance extracting from the renal cortex participates in the development of the vascular lesions.

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We have already elucidated that the vascular permeability of large and medium-sized arteries in different sites vary in pattern and intensity. Therefore, when the development of atherosclerosis was considered from the standpoint of vascular permeability, there might be some difference in atherogesis between intracranial artery and aorta and/or coronary artery.
In this study, in addition to the permeability pattern of aorta and intracranial artery already reported, rabbit coronary artery was examined in respect to the fine structure and permeability pattern by using protein tracers.
1) As a distinct feature of coronary artery was there frequent presence of fenestration in the internal elastic lamina and this might contribute to the more enhanced permeability, especially by virtue of junctional transport, than aorta.
2) Long term subcutaneous injection of epinephrine induced the intimal thickening composed of smooth muscle cells where junctional transport was slightly enhanced.
3) Cholesterol feeding for 1 week, induced the enhanced junctinal transport.
4) Long term cholesterol feeding induced the foam cell lesions where both junctional and vesicular transport were enhanced.

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Numerous foam cells containing much lipid are observed in the intima of human and experimental atherosclerotic lesions. To elucidate the origin of such foam cells, that is, to clarify through what route the intracellular lipid is deposited in the intima, light and electron microscopies were performed with the human aorta and arteries of rabbits given 1% cholesterol diet.
The intima of the human aorta contained smooth muscle cells-derived foam cells with basement membrane, myofilaments and dense bodies, hematogenic large foam cells with numerous lipid vacuoles, monocytes having a kidney shaped nucleus and lysosomes but no lipid vacuoles, and lymphocytes.
These monocytes were not inherent in the intima but had invaded here from circulaling blood. They are considered to phagocytize lipid which insudated into the intima, to turn into foam cells.
In the aorta of rabbits fed on cholesterol diet there were two kinds of foam cells-those lacking the traits of the smooth muscle cell and containing large lucid lipid vacuoles and electron dense lipid granules and those having the traits of the muscle cell. Light and electron microscopy and a Häutchen preparation of rabbit's artery presented a picture of foam cells migrating into the subendothelium through endothelial cell junction. Also foam cells were demonstrated in the blood both light and electron microscopically. It is consequently assumed that some of the foam cells in the intima may be derived from the circulating blood.
As to the derivation of the lipid in the arterial intima, the above described facts suggest that not only the insudation of plasma lipoprotein and lipid synthesis in the intimal cells, but also transportation of lipid into the intima by the blood foam cells may be responsible. In atherosclerotic lesions of human and cholesterol-given rabbits, there are two kinds of foam cells. One is smooth muscle cell-derived, and the other, blood-derived. As to the origin of intimal foam cells derived circulating blood, the following two possibilities are considered: Circulating macrophages phagocytize lipids in blood plasma and pass across the endothelium as foam cells; monocytes migrate from the blood into the vascular wall and phagocytize the lipids which insudated into the intima and turn into foam cells. The conversion of blood-derived mononuclear cells into foam cells was observed in an experiment in which hypercholesterolemic plasma was injected into the rabbit's cornea. In this case, the cornea was first infiltrated by mononuclear cells and polymorphonuclear leukocytes, and with the lapse of time numerous foam cells came to be observed. These foam cells seemed to be derived from blood mononuclear cells, which had phagocytized the lipids at the site of injection.

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It has been first shown by the author and his collaborators (1972) that the strong contracting and swallowing activity of arterial endothelial cells is elicited by various active agents and meets the requirements for the cliteria as the key mechanism in atherogenesis and thrombogenesis.
In this experiments with 65 rabbits, the author administered intravenously the carbon particles with a size of prebetalipoprotein and then visualized the transportation of them by the contracting and swallowing activity of endothelial cells from the blood stream into the aortic wall serially sacrificing the animals thereafter. As a carbon particle, 50% Perikan ink diluted in saline was used mixed with or without angiotensin II (10μg/kg). At five and thirty minutes after injection of the carbon suspension in a dose of 5ml per kg, the aorta of rabbits was fixed by 2.5% glutaraldehyde, which was directly given to the aortic lumen as a perfusate by a catheter inserted surgically into the aorta through the left ventricle under the urethane anaesthesia and subjected to the electron and light microscopical observations.
The formation of nuclear pinch and the statistically significant decrease in the size of tightly contacting parts (gap junction, Hüttner 1973) of intercellular junctions of the endothelial cells due to their contraction were seen 5 and 30 minutes after the carbon challenge (P<0.01, P<0.01). In specimens sampled 5 minutes after the challenge, some carbon particles were found in the endothelial cells and their intercellular junctions were partially widened. In specimens sampled 30 minutes after the challenge, many carbon particles were transported by some group of endothelial cells by the membrane flow and membrane vesiculation (Bennett 1956) and also by widened intercellular junction from the blood stream to the subendothelial space. Such a contracting and swallowing activity seems somewhat exaggerated by the concomitant injection of angiotensin II, but not much. Just two intercellular jnnctions were thus found to have been opened and carbon particles were found in the opened junctions. However the further transportation of carbon particles through holes of the internal elastic lamina seemed almost impossible and in animals sacrificed 2 days after the challenge and even in animals sacrificed 40 days after the challenge the carbon particles still remained almost unchanged in almost the same amount in the subendothelial space surrounded by smooth muscle-like cells. It is also important to note that the entry of carbon particles takes place predominantly in the well known susceptible parts of the arterial system to atherosclerosis. Namely in such parts of the aorta, the trunks of coronary artery, but no entry of carbon particles was found in the artery of circulus Willissi in young rabbits. (In another experiments in rats and dogs, which are nonsusceptible animals to atherosclerosis, no carbon particles enter the subendothelial space by the same challenge with carbon and angiotensin II.)
Endothelial-cell relaxants, EG467 (1 and 10mg/kg p. o.) and EG626 (0.1 and 1.0mg/kg p. o.) exhibited a striking preventive effect against the contracting and swallowing activity of endothelial cells elicited by the carbon challenge or the carbon and angiotensin II challenge. The formation of nuclear pinch was prevented and the tightly contacting parts of the intercellular junctions was statistically significantly enlarged by relaxing effect of those substances and the carbon entry was strikingly prevented by EG467 (1mg/kg and 10mg/kg p. o.) and especially powerfully by EG626 (0.1mg and 1mg/kg p. o.).
The subendothelial entry of carbon particles was also photographed by light microscope in the whole luminal surface of thoracic or abdominal segments of the aortas, in which the aortic lumen was carefully washed in situ by saline and then fixed by a standard formaldehyde fixative and the amount of carbon particles entere

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Xe-133クリアランス法による虚血後反応性充血時血流量 (RBF) 測定法について, 1) 再現性の検討, 2) 閉塞性動脈硬化症患者の1年間の自然経過, 3) 閉塞性動脈硬化症46肢と正常下肢20肢についてのRBF測定成績, 4) 潜伏時間とRBF, 5) 趾尖容積脈波とRBF, 6) Pyridinolcarbamate 投与前後のRBFと臨床症状等, について検討した. その結果再現性は良好で, 正常者と患者では有意の差を示し, 趾尖容積脈波との一致を示し, 治療による症状の改善とRBFの増加はよく一致していた.

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