Involvement of urotensin II in the progression of atherosclerosis

1.我们最近分离出一种新的家兔品系，命名为TGH，其血浆甘油三酯和胆固醇水平严重升高。本研究的目的是探讨动脉粥样硬化的进展和血流动力学参数在TGH兔。用氯胺酮和甲苯噻嗪麻醉日本白色（JW）和TGH家兔（24-27月龄）。JW和TGH家兔的甘油三酯血浆浓度分别为63.1 ± 8.0和446.0 ± 35.2 mg/dL。通过植入股动脉的导管测量血压。组织学检查采用苏木精-伊红和弹力纤维-Masson三色染色检测动脉粥样硬化病变。JW兔没有动脉粥样硬化病变。在TGH兔，严重的动脉粥样硬化病变观察到整个主动脉，特别是在主动脉弓。股动脉基础压之间没有显着差异JW和TGH兔。TGH组基础脉压（48.3 ± 4. ...更多信息 JW兔的平均动脉压（28.0 ± 5.6mmHg）明显高于JW兔（P <0.05）。静脉滴注L-硝基精氨酸甲酯（L-NAME）可使TGH和JW家兔血压升高。两种家兔对L-NAME的反应无显著差异。本研究表明，严重的动脉粥样硬化的变化发展在TGH兔，并建议，合并动脉粥样硬化是一个重要的因素，促进动脉粥样硬化在TGH兔。TGH家兔的脉压增大可能是由于动脉粥样硬化引起的血管僵硬度增加。TGH系兔遗传性高脂血症将成为研究高脂血症在动脉粥样硬化及动脉粥样硬化相关疾病中的作用的一个有用的动物模型。尾加压素II可诱导大鼠主动脉平滑肌收缩，且其收缩作用随年龄的增长而减弱。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，可能在减少血管收缩中起作用，特别是在年轻的主动脉中。尾加压素II受体的表达随增龄而降低。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