HYPOTHALAMIC CONTROL OF VENOUS CAPACITANCE

有相当多的证据表明交感神经系统控制 静脉电容在心血管疾病中起着重要作用， 体内平衡 同样，大量证据表明， 中枢神经系统（CNS）控制交感神经流出到 心血管系统 但是，直接的数据相对较少 研究CNS对静脉功能的控制。 拟议的研究是 旨在检验室旁核的假设， 下丘脑（PVN）在控制静脉 功能 PVN对静脉功能的影响将在 三个水平;整个清醒动物，孤立的血管床和 单个微静脉。 该提案的目标是：1） 确定室旁核的激活是否 下丘脑（PVN）影响平均循环充盈压（MCFP） 和清醒大鼠的全身压力-容积关系，2） 描述这些反应中涉及的血流动力学机制，3） 描述所涉及的神经和体液效应机制，4） 确定局部血管床（内脏与骨骼肌） 电容响应和这些响应中涉及的机制，以及 5)确定PVN刺激对压力直径的影响 内脏和骨骼肌中单个静脉的关系 血管床 这些目标将通过测量动脉和静脉血压来实现， 心输出量和局部血流量。 在清醒大鼠中，MCFP将 用作静脉张力的指标，并将根据动脉 以及心输出量短暂中断后的静脉压。 将构建MCFP-血容量曲线以分析系统性 压力-体积关系 MCFP将在激活期间确定 手术前后PVN的变化（例如，肾上腺髓质切除术）和 药理学的（例如，α肾上腺素受体阻断）干预。 在 体内恒流灌注血管床制剂将用于 确定局部静脉电容响应，并确定 有助于静脉电容效应的血液动力学机制 PVN激活。 最后，直接测量微静脉压 将使用伺服零位压力测量进行直径测量 和体内显微镜检查来评估PVN刺激对 单个静脉中的压力-容积关系。 拟议的研究采用多方面的方法， 研究室旁核在控制静脉容量中的功能作用 三个层次的血管组织。 这些研究将提供 关于CNS控制静脉功能的有意义的新信息。 由于静脉功能改变，因此该信息具有临床相关性 在人类高血压患者和某些中枢作用的抗高血压药物中 药物（例如，可乐定）可影响静脉电容。 此外，本发明还提供了一种方法， 静脉系统参与对压力的心血管反应， 然而，中枢神经系统的网站和机制仍有待阐明。 建议的研究将为未来的研究提供重要的背景数据。 研究旨在解决这些问题。

There is considerable evidence that sympathetic nervous system control of venous capacitance plays an important role in cardiovascular homeostasis. Similarly, a good deal of evidence indicates that the central nervous system (CNS) controls sympathetic outflow to the cardiovascular system. However, there is relatively little data directly investigating CNS control of venous function. The proposed research is designed to test the hypothesis that the paraventricular nucleus of the hypothalamus (PVN) plays an important role in the control of venous function. The effects of the PVN on venous function will be studied at three levels; whole conscious animals, isolated vascular beds and individual microvenules. The goals of the proposal will be to: 1) determine if activation of the paraventricular nucleus of the hypothalamus (PVN) influences mean circulatory filling pressure (MCFP) and the systemic pressure-volume relationship in the conscious rat, 2) characterize the hemodynamic mechanisms involved in these responses, 3) characterize the neural and humoral effector mechanisms involved, 4) determine the regional vascular bed (splanchnic versus skeletal muscle) capacitance responses and the mechanisms involved in these responses, and 5) determine the effects of PVN stimulation on the pressure-diameter relationships in individual veins in the splanchnic and skeletal muscle vascular beds. These goals will be met by measuring arterial and venous blood pressures, cardiac output and regional blood flow. In conscious rats, MCFP will be used as an index of venous tone and will be calculated from the arterial and venous pressures following a brief interruption of cardiac output. MCFP-blood volume curves will be constructed to analyze the systemic pressure-volume relationship. MCFP will be determined during activation of the PVN before and after surgical (e.g., adrenal medullectomy) and pharmacological (e.g., alpha adrenoreceptor blockade) interventions. In vivo constant-flow perfused vascular bed preparations will be used to determine the regional venous capacitance responses and determine the hemodynamic mechanisms that contribute to the venous capacitance effects of PVN activation. Finally, direct measurement of microvenular pressures and diameters will be carried out using servo-null pressure measurements and in vivo microscopy to assess the effect of PVN stimulation on the pressure-volume relationships in individual veins. The proposed research uses a multifaceted approach to systematically study the functional role of the PVN in the control of venous capacitance at three levels of vascular organization. These studies will provide meaningful new information regarding CNS control of venous function. This information is clinically relevant since venous function is altered in human hypertensives and certain centrally acting antihypertensive drugs (e.g., clonidine) may influence venous capacitance. In addition, the venous system participates in the cardiovascular responses to stress, however, the CNS sites and mechanisms involved remain to be elucidated. The proposed studies will provide important background data for future studies aimed at addressing these questions.