Horio T, Kohno M, Murakawa K, Yasunari K, Yokokawa K, Ueda M, Takeda T
First Department of Internal Medicine, Osaka City University Medical School, Japan.
Atherosclerosis. 1991 Aug;89(2-3):239-46. doi: 10.1016/0021-9150(91)90065-b.
This study examined the influence of hypercholesterolemia on the concentration of plasma immunoreactive (ir) endothelin-1 in rats. Plasma ir-endothelin-1, total cholesterol, triglycerides, and lipoprotein fraction concentrations were measured in three groups of rats; ie, fed a standard diet, a high cholesterol diet, or a high cholesterol diet supplemented with the antihypercholesterolemic drug clinofibrate for 4 and 8 weeks. In the rats fed cholesterol for 8 weeks, morphological changes in thoracic and abdominal aortas were examined. Plasma total cholesterol, low density lipoprotein (LDL), very low density lipoprotein (VLDL) and ir-endothelin-1 concentrations increased significantly in the cholesterol-fed rats after both 4 and 8 weeks. In the clinofibrate-treated rats, these lipid parameters and plasma ir-endothelin-1 levels after 4 and 8 weeks were significantly lower than in the cholesterol-fed rats. The plasma ir-endothelin-1 concentration was correlated with plasma total cholesterol, LDL, and VLDL concentrations in the three study groups after 4 and 8 weeks. Morphologically, neither foam cells formation nor intimal thickening was observed in rats fed the high cholesterol diet for 8 weeks. These observations indicate that hypercholesterolemia without atherosclerosis elevates the plasma ir-endothelin-1 level in rats. The observed increase in plasma ir-endothelin-1 associated with hypercholesterolemia may play a role in the initiation or development of atherosclerotic vascular lesions.
本研究检测了高胆固醇血症对大鼠血浆免疫反应性（ir）内皮素-1浓度的影响。测定了三组大鼠的血浆ir-内皮素-1、总胆固醇、甘油三酯和脂蛋白组分浓度；即分别给予标准饮食、高胆固醇饮食或添加抗高胆固醇血症药物氯贝丁酯的高胆固醇饮食，持续4周和8周。对喂食胆固醇8周的大鼠，检查了胸主动脉和腹主动脉的形态学变化。喂食胆固醇4周和8周后，喂食胆固醇的大鼠血浆总胆固醇、低密度脂蛋白（LDL）、极低密度脂蛋白（VLDL）和ir-内皮素-1浓度均显著升高。在氯贝丁酯治疗的大鼠中，4周和8周后的这些血脂参数和血浆ir-内皮素-1水平显著低于喂食胆固醇的大鼠。在三个研究组中，4周和8周后血浆ir-内皮素-1浓度与血浆总胆固醇、LDL和VLDL浓度相关。形态学上，喂食高胆固醇饮食8周的大鼠未观察到泡沫细胞形成或内膜增厚。这些观察结果表明，无动脉粥样硬化的高胆固醇血症会升高大鼠血浆ir-内皮素-1水平。观察到的与高胆固醇血症相关的血浆ir-内皮素-1升高可能在动脉粥样硬化血管病变的起始或发展中起作用。
