ERECTILE DYSFUNCTION DUE TO ATHEROSCLEROSIS

动脉粥样硬化引起的勃起功能障碍

• 批准号: 2144335
• 负责人: KAZEM M AZADZOI
• 金额: $ 8.3万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-04-10 至 1997-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2144335
• 关键词: atherosclerosis; electromyography; electrostimulus; guanosine monophosphate; hypercholesterolemia; impotence; laboratory rabbit; microcirculation; muscle tone; nitric oxide; pathogenic diet; penis disorder; penis erection; radioimmunoassay; reproductive system circulation; vascular endothelium; vascular smooth muscle; vein occlusion

The general aim of the proposal is to study the pathogenesis and pathophysiology of hypercholesterolemia or atherosclerosis-induced impotence. The effects of hypercholesterolemia or atherosclerosis on the reactivity of corporal smooth muscle, corporal endothelium, penile cavernosal arteries and cellular mechanism of muscle relaxation will be investigated. Majority of cases of impotence due to corporal veno-occlusive dysfunction are associated with vascular risk factors such as smoking, hypercholesterolemia, atherosclerosis and hypertension. The pathogenesis and pathophysiology of atherosclerotic impotence have not been investigated. The proposed study will lead to improved understanding of the effects of hypercholesterolemia or atherosclerosis on the physiology of erectile tissue and has the potential to provide great information on the fundamental mechanisms of erectile dysfunction. Identification of the physiologic alterations in erectile tissue due to hypercholesterolemia or atherosclerosis may lead to improved diagnosis and more effective treatment of organic erectile dysfunction. The animal model of atherosclerotic impotence is developed by balloon deendothelialization of the iliac arteries and providing a cholesterol-rich diet (0.5% cholesterol and 4% peanut oil). In the proposed study, the New Zealand white rabbits will be randomly divided into four groups: 1) ballooned cholesterol diet, 2) ballooned regular diet, 3) cholesterol diet alone and 4) regular diet alone. At week 10, 20, 30 or 40, in all animals, erectile response to electrical stimulation of the pelvic nerve or intracavernosal injection of papaverine and phentolamine will be examined. The function of corporal veno-occlusion will be evaluated with dynamic infusion cavernosometry and cavernosography. Impotent animals including those with corporal veno-occlusive dysfunction will be identified. After this the animals will be sacrificed with intravenous injection of pentobarbital and the corporal tissue will be isolated for further studies. To study the effects of hypercholesterolemia or atherosclerosis on corporal smooth muscle tone, reactivity of corporal smooth muscle and endothelium, release of nitric oxide and accumulation of cyclic guanosine monophosphate (cGMP) in the corporal tissue will be compared between the four groups. The reactivity of corporal smooth muscle and corporal endothelium will be studied in the organ bath. The release of nitric oxide and accumulation of cGMP in the corporal tissue during muscle relaxation will be determined with radioimmunoassay. To study the effects of hypercholesterolemia or atherosclerosis on the physiology of penile microvasculature, alterations in the reactivity of cavernosal arteries will be examined in the wire myograph. All results will be compared between the four groups in an attempt to establish a relationship between the in vivo and in vitro parameters of erectile dysfunction.

该提案的一般目的是研究发病机理和 高胆固醇血症或动脉粥样硬化诱导的病理生理学 阳ot。 高胆固醇血症或动脉粥样硬化对 体平滑肌，下皮，阴茎的反应性 海绵体动脉和肌肉放松的细胞机制将是 调查。 大多数由于下士而阳ot的案件 静脉固定功能障碍与血管危险因素有关 作为吸烟，高胆固醇血症，动脉粥样硬化和高血压。 这 动脉粥样硬化阳性的发病机理和病理生理学尚未 被调查。 拟议的研究将改善 了解高胆固醇血症或动脉粥样硬化的影响 关于勃起组织的生理学，并有可能提供 有关勃起功能障碍的基本机制的大量信息。 鉴定由于勃起组织的生理改变 高胆固醇血症或动脉粥样硬化可能会改善诊断 以及对有机勃起功能障碍的更有效治疗。 动物 动脉粥样硬化阳ot的模型是由气球开发的 叶叶动脉的除去皮层化并提供 富含胆固醇的饮食（0.5％胆固醇和4％花生油）。 在 拟议的研究，新西兰白兔子将被随机划分 分为四组：1）气囊胆固醇饮食，2）常规气囊 饮食，3）单独胆固醇饮食，4）单独饮食。 在第10周， 在所有动物中，20、30或40，对电刺激的勃起反应 骨盆神经或丘内肠肠内注射的 将检查苯丙胺。 下士静脉牙菌概括的功能 将通过动态输注海绵体测定法和 海绵体学。 无能的动物，包括有生产的动物 将确定静脉固定功能障碍。 之后，动物 将通过静脉注射戊巴比妥和 体育组织将被隔离以进行进一步研究。 研究 高胆固醇血症或动脉粥样硬化对体光滑的影响 肌肉张力，平滑肌和内皮的反应性， 一氧化氮的释放和循环鸟嘌呤的积累 将比较体组织中的单磷酸（CGMP） 四组。 体平滑肌和下士的反应性 内皮将在器官浴中进行研究。 一氮的释放 在肌肉期间，氧化物和CGMP的积累 放松将通过放射免疫测定法确定。 研究 高胆固醇血症或动脉粥样硬化对生理的影响 阴茎微举行，海绵体反应性的改变 动脉将在钢丝线肌电图中检查。 所有结果将是 比较这四个小组，以建立一个 勃起的体内和体外参数之间的关系 功能障碍。