Nicotine이 cholesterol 食餌性 家兎動脈硬化症에 미치는 影響

Abstract

[한글]

[영문]

Nicotine is known to have peripheral vasoconstrictive effect through the stimulation of the adrenal medulla and sympathetic ganglia to Produce nor-epinephrine (Haimovici 1948). It is also known for some time that smoking is an important factor in the etiology and the progression of thromboangitis obliterans (Buerger's disease) and Raynaud's disease. Some authors believe that smoking causes thromboangiitis while others regard smoking as a promoting factor in the progression of the disease. regardless its etiological role in the development of thromboangiitis obliterans it is well proved that without cessation of smoking the condition is not easily amenable.

The mechanism by which smoking bring about ill-effect on thromboangiitis obliterans is not clear. Sulzberger (1934) demonstrated vascular hypersensitivity to the components of tobacco extracts other than nicotine, whereas many others

believe that ill-effect of the smoking is due to the action of nocotine in the tobacco.

Huper (1943) examined the histologic chanties following a Prolonged administration of nicotine in rats and dogs. He found that nicotine causes degenerative changes in the vascular system similar to those induced by the administration of epinephrine. Therefore, the present investigation is undertaken to study the effects of nicotine upon cholesterol-induced athero-sclerosis on the assumption that nicotine might enhance atheroma formation.

Materials and Methods

Albino rabbits of around 1.8 kg were divided into 8 groups and treated as follows:

Group Ⅰ : 10 rabbits, given 1 ml of saline per kg plus 1 gm of cholesterol per day.

Group Ⅱ : 6 rabbits, 1 mg of nicotine per kg.

Group Ⅲ : 10 rabbits, 1 mg of nicotine per kg plus 1 gm of cholesterol.

Group Ⅳ : 6 rabbits, 3 mg of nicotine per kg.

Group Ⅴ : 10 rabbits, 3 mg of nicotine per 1g plus 1 gm of cholesterol.

Group Ⅵ : 6 rabbits, 5 mg of nicotine per kg.

Group Ⅶ : 10 rabbits, 5 ml of saline per kg plus 1 gm of cholesterol.

Group Ⅷ : 6 rabbits, 1 mg of nicotine per kg.

Animals were fed with 300 gms of bean-curd residue Per day. Cholesterol was given mixed with a small amount of bean-curd residue once a day at early in the morning. Nicotine (Eastman Kodak product, 97% pure) was diluted in saline in three different

concentration to contain 1 mg/ml, 3 mg/ml, and 5 mg/ml, and was given to respective group in respective dose intraperitoneally once a day. Total experimental period lasted for 60 days.

During the experimental period, body weight was measured at every 10 days, and serum cholesterol and phospholipids level once every 30 days.

After 60 days of cholesterol and nicotine administration, animals were killed by air embolism. The aortas were removed and Sudan Ⅳ staining was applied to estimate the degree of gross atheroma formation. Sections from the ascending, thoracic and

abdominal portions of the aortas, coronary arteries, carotid arteries, cerebral arteries, renal arteries, femoral arteries, pulmonary arteries, liver, adrenals, spleen, and thyroid glands were taken after the fixation in 4% neutral formalin. Microsections were prepared in 6 μ thickness after paraffin embedding. All Sections were stained with hematoxylin-eosin and special stainings were made as required.

Microscopical studies included the degree and picture of atheroma formation in the aorta, coronary arteries, carotid arteries, cerebral arteries, renal arteries, femoral arteries and pulmonary arteries. And the degree of lipidosis in the liver

was also examined.

Results and Summary

Serum cholesterol increased rather sharply during the first 30 days, but the increase was insidious in spite of continuous feeding of cholesterol thereafter.

The smaller dose of nicotine showed enhancing effect on hypercholesterolemia while the larger dose has rather depressing effect. The level of serum phospholipids increased in parallel to cholesterol level as a whole, but the administration of nicotine showed slightly depressing effect reciprocally to the dose of nicotine given.

The degree of gross atheroma formation in the aorta was markedly reduced in the groups treated together with nicotine. The degree of inhibition on atheroma formation was parallel to the dose of nicotine administered. Microscopical studies of the aortas and other arteries showed lesser degree of atheroma formation in the aorta among the groups treated with nicotine, However, the degree of atheroma formation in the coronary, renal and femoral arteries were not notably different between experimental groups, whereas the atheroma formation in the pulmonary artery and choroid plexus of the brain was inhibited by larger dose of nicotine.

The changes of vascular wall due to the administration of nicotine alone consisted of necrosis, degeneration of elastic fibers, cystic changes and calcification of the media of the aorta, and endothelial hyperplasia with hyaliniation of the media in smaller arteries.

Nicotine also showed slight but definite inhibiting effect on the lipids deposition in the liver.

In summary, on the contrary to an original assumption that nicotine might have enhancing effect on cholesterol induced atherosclerosis in rabbits, the results obtained by present experiment showed inhibiting effect of nicotine on cholesterol-induced atheroma formation. The mechanism by which nicotine inhibited atheroma formation is not clear, but it may be due to mobilizing action of tissue fat, despression of serum phospholipids level, and perhaps stabilizing erect of nicotine on blood lipids.