ERECTILE DYSFUNCTION DUE TO ATHEROSCLEROSIS

动脉粥样硬化引起的勃起功能障碍

• 批准号: 3464692
• 负责人: KAZEM M AZADZOI
• 金额: $ 12万
• 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/3464692
• 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.

该提案的总体目标是研究发病机制和 高胆固醇血症或动脉粥样硬化引起的病理生理学 阳痿。 高胆固醇血症或动脉粥样硬化对身体的影响 下体平滑肌、下体内皮、阴茎的反应性 海绵体动脉和肌肉松弛的细胞机制将是 调查了。 大多数阳痿病例是由于下士造成的 静脉闭塞功能障碍与血管危险因素有关，例如 如吸烟、高胆固醇血症、动脉粥样硬化和高血压。 这 动脉粥样硬化性阳痿的发病机制和病理生理学尚未 被调查。 拟议的研究将导致改进 了解高胆固醇血症或动脉粥样硬化的影响 勃起组织的生理学，并有可能提供 有关勃起功能障碍基本机制的大量信息。 识别勃起组织的生理变化 高胆固醇血症或动脉粥样硬化可能会改善诊断 更有效地治疗器质性勃起功能障碍。 动物 利用球囊建立动脉粥样硬化性阳痿模型 髂动脉去内皮化并提供 富含胆固醇的饮食（0.5%胆固醇和4%花生油）。 在 拟议的研究中，新西兰白兔将被随机分组 分为四组：1）气球胆固醇饮食，2）气球常规饮食 饮食，3）单独的胆固醇饮食和4）单独的常规饮食。 第 10 周时， 20、30 或 40，所有动物对电刺激的勃起反应 盆腔神经或海绵体内注射罂粟碱和 将检查酚妥拉明。 下体静脉阻塞的功能 将通过动态输注海绵体测量进行评估 海绵体造影。 阳痿动物，包括下士动物 将识别静脉闭塞功能障碍。 此后动物们 将通过静脉注射戊巴比妥处死 身体组织将被分离以供进一步研究。 为了研究 高胆固醇血症或动脉粥样硬化对下体平滑肌的影响 肌张力、下体平滑肌和内皮细胞的反应性， 一氧化氮的释放和环鸟苷的积累 身体组织中的单磷酸盐（cGMP）将在 四组。 下体平滑肌和下体的反应性 内皮细胞将在器官浴中进行研究。 硝酸的释放 肌肉生长期间体内组织中cGMP的氧化物和积累 松弛将通过放射免疫测定来确定。 为了研究 高胆固醇血症或动脉粥样硬化对生理学的影响 阴茎微血管、海绵体反应性的改变 将通过钢丝肌动描记器检查动脉。 所有结果将是 比较四组之间的差异，试图建立一个 体内和体外勃起参数之间的关系 功能障碍。