DOCA高血圧ラットの心血管病モデルにたいする4-0-メチルアスコクロリン (MAc) の作用

Abstract

Epidemiologic evidences have been accumulated that lipid metabolism becomes abnormal not only in atherosclerosis but also arterio-/arteriolosclerosis. However, lipid metabolism in Hypertension has not so far been attracted much attention. This report deals with lipid metabolism in hypertensive rats induced by deoxycorticosterone acetate (DOCA) and 1% NaCl, together with the effect of a fungal prenylphenol, 4-o-methyl ascochlorin (MAc), an experimental hypolipidemic agent.Unilateral nephrectomized rats, when treated with DOCA and NaCl for 7 weeks, became hyperlipidemia accompaning with hypertension without loading dietary lipid. The most striking correlation existed between the serum cholesterol and renal weight (r=0.9148). Therefore, we consider that renal abnormality in electrolyte metabolism is capable of inducing hyperlipidemia.Ring like fat deposition were observed at mesenteric arteries in DOCA-hypertensive rats. Pathological change of mesenteric arteries was increased associated with elevating blood pressure. When hypercholesterolemia was induced, more fat deposited.Fibrous thickening and fibrinoid degeneration were observed at renal arteries in DOCA-hypertensive rats. Degree of arterial injury in the rats fed on lipid rich diet was more seveare than in rats fed on normal diet.Cholesterol content in aortas is not usually affected by serum cholesterol level alone in rats. Although when lipid rich diet was loaded, it was not increased. But in DOCA-hypertension, cholesterol in aortas was increased upto as twice high as that of the normal without any supply of excess dietary fat. These experimental evidences suggest that increased aortic cholesterol content related to hypertention, hyperlipidemia and aortic hypertrophy. Among these factors, aortic hypertrophy showed the highest correration (normal diet r=0.9514, lipid rich diet r=0.9426).In DOCA-hypertensive rats either fed on normal or lipid rich diet, triglyceride content in aortas significantly reduced as compared with the corresponding normal. An alternative possibility that DOCA-hypertension causes altered energy metabolism leading to preferential utilization of fatty acids, thus resulting in decrease of triglyceride storage.These alteration was prevented by treating with MAc, an experimenal hypolipidemic agent.