Chinellato A, Ragazzi E, Pandolfo L, Alvano A P, Froldi G, De Biasi M, Caparrotta L, Aliev G, Fassina G
Department of Pharmacology, University of Padova, Italy.
J Cardiovasc Pharmacol. 1994 Aug;24(2):216-28.
We investigated serum and aortic tissue lipid content, in vitro aortic response to drugs, and morphology of thoracic aorta in Pittsburgh Yoshida rats (YOS), a new animal model of endogenous hyperlipidemia. Experiments were performed on 2-, 6-, and 18-month-old rats. Normolipidemic Brown Norway rats (BN) were used as controls. Both serum cholesterol and triglycerides increased significantly with age in YOS rats, but remained constantly low in the control group. In YOS rats, absolute serum concentration of high density lipoprotein (HDL)-cholesterol increased significantly with age, although HDL-cholesterol/total-cholesterol ratio decreased. In contrast, no difference in cholesterol content in aortic tissue was detected between the two animal strains or among different age groups. The contractile force generation of thoracic aorta to norepinephrine (NE) and serotonin increased with age in both strains of animals. The endothelium-dependent relaxation induced by acetylcholine (ACh) was significantly reduced in 6- and 18-month-old YOS as compared with 2-month-old YOS but not in BN. ATP-induced relaxation was significantly impaired in YOS thoracic aorta. In contrast, the relaxation induced by NaNO2 acting in smooth muscle did not vary with age in either YOS or BN. Only alterations in endothelial cells, not typical atheromatous injuries in thoracic aorta wall were detected in YOS even at age 18 months. Our data indicate that despite high serum lipid levels, YOS do not develop typical atheromatous lesions or functional and morphologic damage of smooth muscle cells in thoracic aorta, whereas YOS show decreased endothelium-dependent relaxation and morphologic alteration of endothelial cells.
我们研究了匹兹堡吉田大鼠（YOS）这一内源性高脂血症新动物模型的血清和主动脉组织脂质含量、主动脉对药物的体外反应以及胸主动脉形态。实验在2个月、6个月和18个月大的大鼠身上进行。血脂正常的棕色挪威大鼠（BN）用作对照。YOS大鼠的血清胆固醇和甘油三酯均随年龄显著升高，但对照组则一直保持在低水平。在YOS大鼠中，高密度脂蛋白（HDL）胆固醇的绝对血清浓度虽随年龄显著升高，但其HDL胆固醇/总胆固醇比值却下降。相比之下，两种动物品系之间以及不同年龄组的主动脉组织胆固醇含量均未检测到差异。两种动物品系的胸主动脉对去甲肾上腺素（NE）和5-羟色胺的收缩力均随年龄增加。与2个月大的YOS相比，6个月和18个月大的YOS中乙酰胆碱（ACh）诱导的内皮依赖性舒张显著降低，但BN中未出现这种情况。YOS胸主动脉中ATP诱导的舒张明显受损。相比之下，YOS和BN中由平滑肌中作用的亚硝酸钠诱导的舒张均不随年龄变化。即使在18个月大时，YOS中也仅检测到内皮细胞改变，而非胸主动脉壁典型的动脉粥样硬化损伤。我们的数据表明，尽管YOS血清脂质水平较高，但并未发生胸主动脉典型的动脉粥样硬化病变或平滑肌细胞的功能及形态损伤，然而YOS表现出内皮依赖性舒张降低以及内皮细胞形态改变。
