ERECTILE DYSFUNCTION DUE TO ATHEROSCLEROSIS

这项建议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的病理生理学 勃起功能障碍。高胆固醇血症或动脉粥样硬化对 阴茎、阴茎和阴茎的反应性 海绵体动脉和肌肉松弛的细胞机制 调查过了。大多数由下体引起的阳萎病例 静脉闭塞功能障碍与血管危险因素相关，如 如吸烟、高胆固醇血症、动脉粥样硬化和高血压。这个 动脉粥样硬化性阳萎的发病机制和病理生理尚未见报道 被调查过了。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 关于勃起组织的生理学，并有可能提供 关于勃起功能障碍的基本机制的大量信息。 勃起组织生理性改变的鉴定 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。这只动物 球囊法制备动脉粥样硬化性阳萎模型 髂动脉去内皮化和提供 高胆固醇饮食(0.5%胆固醇和4%花生油)。在 建议研究，将新西兰大白兔随机分为 分为四组：1)高胆固醇饮食，2)高胆固醇饮食 饮食，3)单独的胆固醇饮食和4)单独的正常饮食。在第10周， 20、30或40岁，在所有动物中，对电刺激的勃起反应 盆神经或海绵体内注射罂粟碱和 将检查酚妥拉明。浅谈体静脉闭塞的作用 将通过动态海绵体测定术和 海绵体摄影术。无能动物，包括那些有下士的 静脉性闭塞功能障碍将被识别。在这之后，动物 将通过静脉注射戊巴比妥和 下体组织将被分离出来进行进一步研究。为了研究 高胆固醇血症或动脉粥样硬化对小体光滑的影响 肌张力，肌体平滑肌和内皮的反应性， 一氧化氮的释放与环鸟苷的蓄积 体部组织中的一磷酸(CGMP)将在 四组。小体平滑肌和小体的反应性 血管内皮细胞将在器官浴中进行研究。硝酸根的释放 肌肉组织中cGMP的氧化和积累 松弛将用放射免疫法测定。为了研究 高胆固醇血症或动脉粥样硬化对心脏生理学的影响 阴茎微血管形成，阴茎海绵体反应性改变 动脉将在钢丝肌电图仪中进行检查。所有结果都将是 在四个组之间进行比较，试图建立一个 勃起功能体内外参数的相关性研究 功能障碍。

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.