N O S AND NEUROPATHIC AND ENDOTHELIAL INDUCED ED

说明(改编自应用程序) 勃起功能障碍(ED)是一种破坏性的病理发展 影响1000-3000万美国男性，造成超过1.5亿美元的损失 仅用于住院泌尿外科护理(1985美元)。糖尿病(DM) 是ED的常见风险因素，因为它影响到1500万美国人和 在50%受影响的男性中会导致勃起功能障碍。这种ED的发病机制是 有争议的原因是混合血管和神经病变 人类糖尿病。最近，我们报道了一种糖尿病动物模型，并提供了证据 支持单独将神经病作为ED的原因。我们发现，使用生物- 饲养Wistar(BBWOR)糖尿病大鼠模型的弥漫性神经病变 导致无混杂血管病变的勃起功能障碍。我们已经确定了 糖尿病患者性行为的严重缺陷以及缺陷 性反射和生理性勃起提示中枢神经系统功能障碍 和并发的弥漫性周围神经病变过程导致 艾德。我们最近有证据表明，一氧化氮(NO)，一种中枢和 外周自主神经递质与阴茎勃起调节 在糖尿病大鼠中降低。我们的目标是描述DM对以下方面的影响 阴茎平滑肌(SM)松弛的自主神经调节我们假设 我们模型中的ED是由于神经的中枢和外周改变所致 没有内容和随后的传输受损。这一变化在没有水平的情况下 在神经和躯体SM中，NOS的表达下调是次要的 纸巾。提出了以下四个具体目标：1)测试 存在多种一氧化氮合酶亚型的假说 在对照组和糖尿病大鼠的阴茎SM和脊髓中应用 免疫印迹和免疫组织化学，2)检验假设 脊髓组织中一氧化氮合酶亚型的含量和表达下调 糖尿病患者的脐带和阴茎水平，3)检验糖尿病患者 降低了一氧化氮合酶活性，改变了次生代谢物的水平 阴茎SM中的信使(CGMP)，以及4)检验他们假设NOS 差异在于中枢神经系统和三叉神经核/阴茎的缺陷 糖尿病大鼠使用一氧化氮合酶拮抗剂诱导糖尿病- 比如对照组大鼠性功能障碍。这项研究的结果将有助于 在理解糖尿病神经病变如何促进性行为方面 对照组大鼠的功能障碍。这项研究的结果将有助于 对糖尿病神经病变如何导致性功能障碍的理解 并阐明了预防它们的可能机制。

DESCRIPTION (adapted from the application) Erectile dysfunction (ED) is a devastating pathologic development affecting 10-30 million American men and costing in excess of $150 million for inpatient urologic care alone (1985 dollars). Diabetes mellitus (DM) is a common risk factor for ED as it effects 15 million Americans and contributes to ED in 50% of affected males. The pathogenesis of this ED is controversial because of the mixed angiopathy and neuropathy found in human DM. Recently, we reported an animal model of DM with evidence supporting neuropathy alone as a cause for ED. We found, using the Bio- breeding Wistar (BBWOR) diabetic rat model, diffuse neuropathic changes resulting in ED without a confounding vasculopathy. We have identified profound deficits in the sexual behavior of diabetics as well as deficits in sexual reflexes and physiologic erections suggesting a CNS dysfunction and a concurrent diffuse peripheral neuropathic process(es) resulting in ED. We have recent evidence that nitric oxide (NO), a central and peripheral autonomic neurotransmitter and regulatory of penile erection, is decreased in diabetic rats. Our goal is to characterize DM's impact on autonomic regulation of penile smooth muscle (SM) relaxation. We postulate that ED in our model is due to a central and peripheral change in neural NO content and subsequent impaired transmission. This change in NO level is secondary to down regulated NOS expression in neural and corporal SM tissues. The following four specific aims are proposed: 1) test the hypothesis that multiple nitric oxide synthase (NOS) subtypes are present in the penile SM and spinal cord of control and diabetic rats using Western immunoblot and immunohistochemistry, 2) test the hypothesis that the content and expression of NOS subtypes are down regulated at spinal cord and penile level in diabetics, 3) test the hypothesis that diabetics have decreased NOS enzymatic activity and altered levels of secondary messengers (cGMP) in the penile SM, and 4) test they hypothesis that NOS deficits in the CNS and the PNS/penis are responsible are the differences seen in diabetic rats by the use of NOS antagonists to induce diabetic- like sexual dysfunction in control rats. Results of this research will aid in the understanding of how diabetic neuropathy contributes to sexual dysfunction in control rats. Results of this research will aid in the understanding of how diabetic neuropathy contributes to sexual dysfunction and elucidate possible mechanisms to prevent them.