Involvement of urotensin II in the progression of atherosclerosis

1.我们最近分离出了一种新的兔品系，命名为TGH，其血浆甘油三酯和胆固醇水平极高。本研究的目的是观察TGH兔动脉粥样硬化的进展和血流动力学参数。日本大白兔(JW)和TGH兔(24-27个月龄)用氯胺酮和赛拉津麻醉。JW和TGH兔血浆甘油三酯浓度分别为6 3.1±8.0和446.0±35.2 mg/dL。通过在股动脉植入导管测量血压。组织学检查采用苏木精-伊红染色和Elastica-Masson三色染色检测动脉粥样硬化病变。JW兔无动脉粥样硬化病变。在TGH兔中，动脉粥样硬化病变严重，尤其是在主动脉弓。基础股动脉压在JW和TGH兔之间无显著差异。而TGH兔的基础脉压(48.3±4.…>5 mm Hg)显著高于JW兔(28.0±5.6 mm Hg)。静脉滴注N、G-硝基-L-精氨酸甲酯(L-NAME)可使TGH和JW兔血压升高。两个品系的兔对L-NAME的反应无显著差异。本研究表明TGH兔出现了严重的动脉粥样硬化改变，提示混合性高脂血症是促进TGH兔动脉粥样硬化的重要因素。TGH兔较高的脉压可能是由于动脉粥样硬化时血管僵硬增加所致。遗传性高甘油三酯血症的TGH兔模型将成为研究高脂血症在动脉粥样硬化发展中的作用以及在许多动脉粥样硬化相关疾病中作用的有用动物模型。尾加压素II可诱导大鼠主动脉血管平滑肌收缩，而尾加压素II诱导的收缩随年龄增长而下降。血管内皮细胞对尾加压素II的反应产生一氧化氮，而不是环氧合酶代谢产物，如前列环素，可能在减轻血管收缩方面发挥作用，尤其是在年轻的主动脉。尾加压素II受体的表达随增龄而降低。较少

1. We have recently segregated a new line of rabbit, named TGH, with severely high levels of plasma triglyceride and cholesterol. The aim of the present study was to investigate the progression of atherosclerosis and haemodynamic parameters in TGH rabbits. Japanese white (JW) and TGH rabbits (24-27 months old) were anaesthetized with ketamine and xylazine. Plasma concentrations of triglyceride were 63.1 ± 8.0 and 446.0 ± 35.2 mg/dL in JW and TGH rabbits, respectively. Blood pressure was measured by a catheter implanted in the femoral artery. Histological examinations were performed using haematoxylin-eosin and elastica-Masson trichrome staining to detect atherosclerotic lesions. The JW rabbits had no atherosclerotic lesions. In TGH rabbits, severe atherosclerotic lesions were observed throughout the aorta, especially in the aortic arch. Basal femoral arterial pressure was not significantly different between JW and TGH rabbits. However, the basal pulse pressure in TGH rabbits (48.3 ± 4. … More 5 mmHg) was significantly greater than that of JW rabbits (28.0 ± 5.6 mmHg). Intravenous infusion of N^G-nitro-L-arginine methyl ester (L-NAME) increased the blood pressure of TGH and JW rabbits. There was no significant difference in the response to L-NAME between the two rabbit strains. The present study shows that severe atherosclerotic changes develop in TGH rabbits and suggests that the combined hyperlipidaemia is an important factor for promoting atherosclerosis in TGH rabbits. The greater pulse pressure in TGH rabbits may be due to the increased vascular stiffness with atherosclerosis. TGH rabbit line of heritable hypertriglyceridaemia will become a useful animal model for studies on the role of hyperlipidaemia in the progression of atherosclerosis and in many atherosclerosis-related diseases.urotensin II can induce vascular smooth muscle contraction in rat aorta, and there was an aging-related decline in the urotensin II-induced contraction. Endothelial production of nitric oxide in response to urotensin II but not cyclooxygenase metabolites such as prostacyclin may play a role in reducing the vascular constriction especially in young aorta. The expression of urotensin II receptor decreased by aging. Less