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血壓이 Cholesterol食餌性 家兎動脈硬化症에 미치는 影響에 關한 硏究

Studies of the Influence of Blood Pressure on the Cholesterol-fed Atherosclerosis in Rabbits

최신의학 1965년 8권 2호 p.49 ~ 63
許準, 金東殖,
소속 상세정보
許準 (  ) - 延世大學敎 醫科大學 病理學敎室
金東殖 (  ) - 延世大學敎 醫科大學 病理學敎室

Abstract


Despite a well known fact that hypertensive patients are subject to a greater degree of atherosclerosis than are comparable normotensive individuals, surprisingly little experimental investigations have been carried out to clarify the causality and mechanisms of the influence of blood pressure on the atherosclerosis. Mo¨nekeberg(1924) and Hick(1933) stated that an elevation of blood pressure produces degenerative and sclerotic changes in the arteries.
Moss et al. (1951), Bronte-Stewart and Heptinstall(1954), Deming et al.(1958) and Fischer and Tapper(1960) reported acceleration of hypercholesteremia and atherosclerotic changes by hypertension induced in cholesterol-fed rabbits and rats. Friedman(1963), by exchange graft of a segment of the aorta to the inferior vena cava and a segment of the vein to the abdominal aorta in normoand hypercholesteremic animals, observed that atherosclerotic changes developed in venous graft to the aorta while the arctic graft to the inferior vena cava failed to develop the change. On the other hand, Moritz and Oldt(1937) through a study of human materials stressed that hypertension is not a cause of arteriosclerosis but a result of it. This controversial viewpoint is still shared by many investigators. Finally, it would be interesting to investigate effect of low blood pressure to atherosclerosis, particularly in view of prevalent application of antihypertensive drugs to hypertensive patients.
Present study is undertaken to investigate the effect of both elevated and lowered blood pressure upon cholesterol-fed atherosclerosis with special reference to the behavior of acid mucopolysaccharides, which is becoming a focus of interest in the genesis of atherosclerosis.
Materials and Methods
Seventy-five albino rabbits, around 2㎏ in body weight, were divided into 6 groups. Group Ⅰ comprised of 5 animals and served as normal untreated control: group Ⅱ of 10 animals were fed chol estorol diet only: group Ⅲ of 20 animals were subjected to renal hypertension followed by cholesterol feeding: group Ⅳ of 10 animals were subjected to only renal hypertension. In group Ⅴ of 20 animals hypotension was induced with ansolysen which was followed by administration of chol esterol, group Ⅵ of 10 animals were subjected to hypotension only.
Base diet was 150 gms. of bean curd residue per day per animal. Cholesterol, Merck Co. product, was fed for 3 months period in dose of 1.5 gm per animal per day. Renal hypertension was induced by two stage method of Page (1955), hypotension was induced by the administration of anso lysen (M & B Co., Britain) in doses of 20-140 ㎎ per animal per day during the period of experiment. Blood pressure estimation was made by ear capsule technique of Grant and Rothschild (1934) every other day. Serum total cholesterol and ester were determined once every 30 days by the method of Bloor (1916). Body weight was measured once a week.
At the end of 3 months, survived animals were sacrificed by air enbolism. The aortas were dissected out and examined grossly and microscopically. The topographic estimation of atherosclerotic change was made by the method of Holman (1958), For the histologic examination, hematoxylineosin staining was applied to all cases. In addition, colloidal-iron method of Rinehart-Abul-Haj (1951) to demonstrate acid mucopolysaccharides, aldehyde-fuchsin staining of Gomori (1950) for elastic tissue, and oil red O staining for lipids were applied in selected cases.
Results and Discussion
The body weight has increased slightly in all groups of animals without significant statistical difference among the groups. At the end of the experiment blood pressure rose from initial 66±2.3 ㎜Hg to 89±1.5 in group Ⅱ, from 68±5.2 to 108±1.6 in group Ⅲ, and from 76±4.79 to 100 ±3.0 in group Ⅵ. It fell from. 77±1.89 to 68±0.62 in group Ⅴ and from 72±1.2 to 61±1.05 in group Ⅵ. These data indicate that renal manupulation apparently produced hypertension, and at the same time cholesterol feeding alone also brought an elevation of the blood pressure to a certain extent.
Serum total cholesterol level elevated from initial value of 21.2±3.6 ㎎% to 1342±134.2 ㎎% in group ⅡI, from 33.1±5.87 ㎎% to 1528±97.04 ㎎% in group Ⅲ, and from 43.9±3.82 ㎎% to 1809±134.9 ㎎% in group Ⅴ. Therefore, the degree of hypercholesteremia was the greatest in group Ⅴ (hypotension and cholesterol feeding) and the least in group Ⅱ (cholesterol feeding only), indicating promoting effect of both hypertension and hypotension in induction of hypercholesteremia.
Incidences and severity of atherosclerotic process in the aorta were the greatest in the group Ⅴ and the least in the group Ⅱ. These results seem to go parallel with the alteration of serum cholesterol Level rather than with the elevation of blood pressure. On the other hand, in group Ⅲ (hypertension followed by cholesterol feeding) atheromatous changes extended into inner part of the media while those of group Ⅱ and Ⅴ were limited mostly at the intima over the internal elastic membrane.
Results of histochemical examinations showed marked increase of acid mucopolysaccharides accumulation in groups Ⅲ and Ⅳ (hypertensive), particularly at subintimal areas, immediately below or adjacent portions of the atheromatous lesions in group Ⅲ. Milder but increased accumulation of acid mucopolysaccharides was also observed in group Ⅱ (cholesterol feeding alone). In groups Ⅴ and Ⅵ (hypotensive), however, the amount of acid mucopolysaccharides was lesser than in group Ⅰ (normal control). The elastic lamellae showed various degree of degenerative changes; such as swelling, fraying or disruption, closely associated with the accumulation of acid mucopolysaccharides in hypertensive groups.
When the breakdown of elastic lamellae, particularly internal elastic membrane, is severe the lipid deposition in the intima spread into the media through disrupted internal elastic membrane. The alteration of elastic lamellae in hypotensive groups, on the other hand, was very negligibile and internal elastic membrane was intact, consequently no evidence of spread of atheromatous change into the media was observed in spite of severe atheromatous change at the intima. The data obtained by histochemical study indicates that hypertension induces degeneration of elastic fibers in the aortic wall followed by increased accumulation of acid mucopolysaccharides and spread of atheromatous process into the deeper portions of the wall. Whereas hypotension did not produce either degeneration of elastic membrane or increase of acid mucopolysaccharides. The most significant role of the internal elastic membrane in the experimental cholesterol atherosclerosis appear to be a limiting barrier to prevent the spread of atheromatous process from the intima to the deeper portion, and this might also be true in human disease.
Summary
Alteration of blood pressure, both elevation and reduction, was induced in rabbits and its effect on the cholesterol-fed atherosclerosis was studied.
Alteration of blobd pressure, either increase or decrease, promoted hypercholesteremia, and accel erated atherosclerotic process in cholesterol-fed rabbits These effect were greater in group of hypotensive, animals, but the extension of atherosclerotic process into deeper part of the aortic wall was noted only in hypertensive group.
Histochemical examinations indicated increased amount of acid mucopolysaccharides resulting from degeneration of elastic lamellae in hypertensive animals, and the degeneration of internal elastic membrane allowed the spread of atheromatous lesions from the intima to media. On the other hand, the amount of acid mucopolysaccharides was rather decreased in hypotensive animals and elastic fibers were not notably altered in spite of greater degree of atheromatous change. Therefore, it seems that destruction of elastic tissue and subsequent accumulation of acid mucopolysaccharides play very important role in atherogenesis particularly in the spread of the process, but it is not a sole factor and some others such as the state of blood flow may also play a significant role.

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