ERECTILE DYSFUNCTION DUE TO ATHEROSCLEROSIS

该提案的总体目标是研究发病机制， 高胆固醇血症或动脉粥样硬化诱导的病理生理学 阳痿 高胆固醇血症或动脉粥样硬化对 阴茎海绵体平滑肌、海绵体内皮、阴茎的反应性 海绵体动脉和肌肉松弛的细胞机制将是 研究了 大多数阳痿的情况下，由于身体 静脉闭塞性功能障碍与血管危险因素有关， 如吸烟、高胆固醇血症、动脉粥样硬化和高血压。 的 动脉粥样硬化性阳萎的发病机制和病理生理学还没有 被调查了 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 对勃起组织的生理作用， 勃起功能障碍的基本机制的伟大信息。 勃起组织的生理改变的鉴定， 高胆固醇血症或动脉粥样硬化可能导致改善诊断 更有效地治疗器质性勃起功能障碍 动物 用球囊扩张法建立动脉粥样硬化性阳萎模型 髂动脉的去内皮化，并提供 富含胆固醇的饮食（0.5%胆固醇和4%花生油）。 在 在拟定研究中，将新西兰白色家兔随机分组 分为四组：1）膨胀胆固醇饮食，2）膨胀常规饮食 饮食，3）仅胆固醇饮食和4）仅常规饮食。 在第10周， 20、30或40，在所有动物中，对电刺激有勃起反应 或海绵体内注射罂粟碱， 将检查酚妥拉明。 体静脉阻断功能 将采用动态灌注海绵体测量法进行评价， 海绵体造影术 阳痿动物，包括那些身体 将确定静脉闭塞性功能障碍。 在此之后，动物 将通过静脉注射戊巴比妥处死， 将分离身体组织以供进一步研究。 研究 高胆固醇血症或动脉粥样硬化对身体平滑肌的影响 肌张力，体平滑肌和内皮的反应性， 释放一氧化氮和积聚环鸟苷 将比较两组之间的身体组织中的cGMP水平。 四组。 海绵体平滑肌和海绵体平滑肌的反应性 将在器官浴中研究内皮。 氮的释放 氧化物和cGMP的积累，在身体组织在肌肉 将用放射免疫测定法测定松弛。 研究 高胆固醇血症或动脉粥样硬化对 阴茎微血管，海绵体反应性改变， 将在钢丝肌描记器中检查动脉。 所有结果都将 在四组之间进行比较，试图建立一个 勃起功能的体内和体外参数之间的关系 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.