ALTERED BLADDER BLOOD FLOW IN IC--ROLE OF NITRIC OXIDE

间质性膀胱炎（IC）的病因和发病机制尚不清楚。 目前的一种理论认为，膀胱可能会发生变化， 另一种则表明膀胱血流量减少 这可能是导致IC症状和膀胱变化的原因。 来自患者膀胱活检检查的初步数据 与IC表明，可能有一氧化氮合酶缺乏， 在这些病人的膀胱里。我们的假设是 一氧化氮途径，无论是缺乏或功能障碍，导致 至少一个IC患者亚组的血流量减少，以及 产生了典型的临床症状。 所描述的研究旨在检验以下假设： 一氧化氮和/或一氧化氮合酶的改变， 定性或定量地，导致膀胱血流减少 这导致了临床和组织学变化， 间质性膀胱炎第一项研究调查了 膀胱中的一氧化氮及其在膀胱调节中的作用 血流第二阶段比较硝酸盐的含量和活性 IC患者与正常人相比， 对照第三组实验比较了 IC患者与正常对照组，均处于静息基础状态， 以及血流随充盈和排空的变化。最后的研究 研究膀胱缺血是否会引起排尿的变化 间质性膀胱炎中观察到的行为和组织学变化。 这些研究将共同确定一氧化氮在膀胱癌中的作用。 血流量，确定是否有不足或减少， IC患者与对照组中一氧化氮途径的功能， 确定IC患者是否具有较低的基线膀胱血流量，或 与对照组相比，对充盈和排空的反应受损，最后 确定膀胱血流量的减少是否会导致这些变化 在IC中观察到的排尿模式和组织学。这些发现采取了 能支持我们最初的假设

The etiology and pathogenesis of Interstitial Cystitis (IC) are unknown. One current theory proposes that there may be alterations in bladder neurotransmitters, and another suggests a decrease in bladder blood flow which may be responsible for the symptoms and bladder changes see in IC. Preliminary data from the examination of bladder biopsies from patients with IC suggests that there may be a deficiency in nitric oxide synthase in the bladder of these patients. Our hypothesis is that alterations in the nitric oxide pathway, either a deficiency or dysfunction, leads to a reduction in blood flow in at least one subgroup of patients with IC, and produces the characteristic clinical picture. The studies to be described are designed to test the hypothesis that alterations in nitric oxide and/or nitric oxide synthase, either qualitatively or quantitatively, lead to a reduction in bladder blood flow which results in the clinical and histologic changes observed in interstitial cystitis. The first studies investigate the localization of nitric oxide in the bladder, and its role in the regulation of bladder blood flow. The second phase compares the content and activity of nitric oxide synthase in the bladder of IC patients as compared to normal controls. The third set of experiments compare the bladder blood flow of IC patients with that of normal controls, both in the resting basal state, and changes in blood flow with filling and emptying. The final studies investigate whether bladder ischemia can produce changes in voiding behavior and histological changes as observed in interstitial cystitis. Together these studies will establish the role of nitric oxide in bladder blood flow, determine whether there is a deficiency or decrease in function of the nitric oxide pathway in IC patients vs. controls, determine whether IC patients have a lower baseline bladder blood flow or impaired response to filling and emptying than controls, and finally determine whether reductions in bladder blood flow can produce the changes in voiding pattern and histology observed in IC. These findings taken together would support our initial hypothesis.