N O S AND NEUROPATHIC AND ENDOTHELIAL INDUCED ED

描述（改编自应用程序） 勃起功能障碍（艾德）是一种破坏性的病理发展 影响了1000万到3000万美国男性，花费超过1.5亿美元 仅用于住院泌尿科护理（1985年美元）。糖尿病（DM） 是艾德的常见风险因素，因为它影响1500万美国人， 导致50%的男性患艾德性勃起功能障碍。这种艾德的发病机制是 有争议的，因为混合血管病和神经病变发现， 人DM。最近，我们报道了糖尿病的动物模型， 支持神经病变单独作为ED的原因。我们发现，使用生物- Wistar（BBWOR）糖尿病大鼠模型，弥漫性神经病变 导致艾德性ED而没有混杂的血管病变。我们已经确定 糖尿病患者性行为的严重缺陷以及 性反射和生理勃起表明中枢神经系统功能障碍 以及并发的弥漫性周围神经病变过程， ED.我们最近有证据表明，一氧化氮（NO），一个中央和 外周自主神经递质和阴茎勃起的调节， 在糖尿病大鼠中减少。我们的目标是描述DM对 阴茎平滑肌（SM）松弛的自主调节。我们推测 在我们模型中，艾德是由于中枢和外周神经系统的变化， 没有内容和随后受损的传输。NO水平的变化 继发于神经和躯体SM中NOS表达下调 组织中提出了以下四个具体目标：1）测试 假设存在多种一氧化氮合酶（NOS）亚型 在对照组和糖尿病大鼠的阴茎SM和脊髓中， Western免疫印迹和免疫组织化学，2）检验假设， 脊髓背角NOS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 NOS酶活性降低， 信使（cGMP）在阴茎SM，和4）测试他们的假设，NOS CNS和PNS/阴茎的缺陷是差异的原因 在糖尿病大鼠中通过使用NOS拮抗剂诱导糖尿病- 就像对照组老鼠的性功能障碍一样。这项研究的结果将有助于 在了解糖尿病性神经病变如何影响性功能方面， 在对照组大鼠中的功能障碍。这项研究的结果将有助于 了解糖尿病神经病变如何导致性功能障碍 并阐明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.