Russell J C, Koeslag D G, Dolphin P J, Amy R M
Department of Surgery, University of Alberta, Edmonton, Canada.
Arteriosclerosis. 1990 Jul-Aug;10(4):658-64. doi: 10.1161/01.atv.10.4.658.
Male rats of the JCR:LA-corpulent strain spontaneously develop atherosclerosis and myocardial lesions if corpulent. The corpulent rats exhibit a marked very low density hyperlipidemia and insulin resistance. The incidence of both vascular and myocardial lesions correlates strongly with the hyperinsulinemia, but not with the hyperlipidemia. Corpulent male rats were chronically treated with nifedipine or acetylsalicylic acid to explore the roles of smooth muscle spasm and platelet activity in induction of the myocardial lesions. Acetylsalicylic acid treatment was associated with no significant changes in fasting glucose, insulin, or lipid concentrations. Nifedipine caused no significant changes in glucose concentration but was associated with mildly increased insulin levels. Treatment with nifedipine resulted in significant decreases in serum triglyceride concentrations. The decreases were confined to longer-chain triacylglycerol molecular species with no change in the concentration of molecular species with 48 or 50 acyl carbon atoms. There was no effect on myocardial lesion frequency with acetylsalicylic acid treatment. In contrast, nifedipine prevented the development of old organized scarred lesions. This effect is similar to that seen with treatments that markedly reduce the insulin resistance. These findings suggest that platelet-initiated thrombus formation is not an important factor in lesion formation in the JCR:LA-cp rat, but that smooth muscle spasm is probably important.
LA肥胖品系的雄性大鼠如果肥胖会自发形成动脉粥样硬化和心肌损伤。肥胖大鼠表现出明显的极低密度脂蛋白血症和胰岛素抵抗。血管和心肌损伤的发生率与高胰岛素血症密切相关，但与高脂血症无关。对肥胖雄性大鼠长期给予硝苯地平或阿司匹林，以探讨平滑肌痉挛和血小板活性在心肌损伤诱导中的作用。阿司匹林治疗与空腹血糖、胰岛素或脂质浓度的显著变化无关。硝苯地平对血糖浓度无显著影响，但与胰岛素水平轻度升高有关。硝苯地平治疗导致血清甘油三酯浓度显著降低。降低仅限于长链三酰甘油分子种类，48或50个酰基碳原子的分子种类浓度无变化。阿司匹林治疗对心肌损伤频率没有影响。相比之下，硝苯地平可防止陈旧性有组织瘢痕病变的发展。这种作用与显著降低胰岛素抵抗的治疗效果相似。这些发现表明，血小板引发的血栓形成不是JCR:LA-cp大鼠病变形成的重要因素，但平滑肌痉挛可能很重要。
