MICROVASCULAR PHYSIOLOGY OF THE LOWER UROGENITAL TRACT

下泌尿生殖道的微血管生理学

• 批准号: 2133735
• 负责人: KEVIN Lenuell BILLUPS
• 金额: $ 7.58万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-09-30 至 1996-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2133735
• 关键词: Leydig cells; Sertoli cells; cell adhesion molecules; electrophysiology; hamsters; inflammation; magnetic resonance imaging; male; microcirculation; microscopy; perfusion; reperfusion; reproductive system; reproductive system circulation; seminal vesicles; vascular smooth muscle nervous control

Many disorders of the lower urogenital tract involve one or more aspects of microvessel failure. Examples of specific disorders include: cryptorchidism, impotence, inflammatory disturbances (i.e. cystitis, orchitis, prostatitis), torsion, and varicocele. I hypothesize that the primary cause for these disturbances involves a decline or loss in vascular function that precedes clinical signs of organ failure. This proposition is supported by a massive body of indirect evidence derived from biochemical, physiological and pathological studies of genitourinary structures in healthy and diseased states. I propose to use the hamster testis as a model to test this hypothesis because its exterior location is particularly well suited for the direct observation of all classes of microvessels by intravital microscopy. Furthermore, the functions of the two parenchymal cell types (Leydig cells = steroidogenesis, tubular Sertoli/germ cells = spermatogenesis) can be assessed independently and simultaneously with indices of vascular perfusion. The vasomotor control of arteriolar tone and capillary perfusion will be manipulated experimentally by: i) electrical stimulation of the spermatic nerve, ii) limiting perfusion pressure or flow in the spermatic artery, and iii) torsion and detorsion of the spermatic cord to provoke ischemia/reperfusion injury. Each form of vasomotor control will be assessed concurrently with parenchymal cell performance to uncover the vascular mechanisms that limit or control the availability of oxygen, tropic hormones, and substrates for steroidogenesis or spermatogenesis. Another objective of these experiments is to combine mapetic resonance imaging techniques with intravital assessments of capillary perfusion and cell performance. The methodologies will be used in parallel experiments to test the feasibility of developing noninvasive methods to estimate both testicular perfusion and the function of Leydig, Sertoli, and/or germ cells during the cycle of the seminiferous epithelium. The results of magnetic resonance perfusion imaging and magnetic resonance spectroscopy provide the potential for developing new clinical procedures to facillitate the diagnosis and improve the medical management of microvessel failure in the human testicle. All of the investigative approaches proposed in this application are expected to offer new insights about the proximate causes of the loss or reduction in testicular function following torsion of the spermatic cord. The experimental strategies are unique in their capacity to develop important new approaches to assess the cellular and molecular basis of vascular failure common to many genitourinary disorders. To my knowledge, no other laboratory possesses the background and skills to integrate intravital and magnetic resonance techniques to "look" inside the testis and assess cell function in situ.

下泌尿生殖道的许多疾病涉及一个或多个方面 微血管失败。 特定疾病的示例包括： 隐齿，阳ot，炎症性障碍（即膀胱炎， 佛观，前列腺炎），扭转和静脉曲张。 我假设 这些干扰的主要原因涉及下降或损失 在器官衰竭临床迹象之前的血管功能。 这 命题得到了大量间接证据的支持 从生化，生理和病理学研究 健康和患病状态的泌尿生殖结构。 我建议 使用仓鼠睾丸作为测试该假设的模型 外部位置特别适合直接观察 在所有类别的微血管中，通过浸没显微镜。 此外， 两种实质细胞类型的功能（leydig细胞= 类固醇生成，管状Sertoli/生殖细胞=精子发生） 与血管指数同时独立评估 灌注。 动脉张力和毛细血管的血管舒缩控制 灌注将通过以下方式通过：i）电气来操纵 刺激精子神经，ii）限制灌注压力或 精子动脉的流动，iii）扭转和催化 精子线引起缺血/再灌注损伤。每种形式 血管舒缩控制将与实质细胞同时评估 揭示限制或控制的血管机制的性能 氧气，热带激素和底物的可用性 类固醇发生或精子发生。 这些的另一个目标 实验是将mapetic共振成像技术与 毛细血管灌注和细胞性能的插入性评估。 这 方法学将在并行实验中用于测试 开发无创方法来估计的可行性 Leydig，Sertoli和/或Germ的睾丸灌注和功能 在生精上皮周期中的细胞。 结果 磁共振灌注成像和磁共振光谱 提供了开发新临床程序的潜力 面对诊断并改善 人类睾丸中的微骨分裂衰竭。 所有调查 预计本申请中提出的方法将提供新的 关于损失或减少损失或减少的直接原因的见解 精子绳扭转后的睾丸功能。 这 实验策略的发展能力是独一无二的 评估细胞和分子基础的重要新方法 许多泌尿生殖器疾病常见的血管衰竭。 对我的 知识，没有其他实验室拥有背景和技能 将插入和磁共振技术整合到内部“看” 睾丸和原位评估细胞功能。