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的重要作用 动态平衡。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。然而，直接提供的数据相对较少 探讨中枢神经系统对静脉功能的调控作用。拟议的研究是 旨在检验这样一种假设，即脑室旁核 下丘脑在静脉控制中起着重要作用。 功能。PVN对静脉功能的影响将在 三个层次：完全清醒的动物，孤立的血管床和 单个微静脉。该提案的目标将是：1) 确定脑室旁核的激活是否 下丘脑(PVN)影响平均循环充盈压(MCFP) 以及清醒大鼠的全身压力-容量关系，2) 描述这些反应所涉及的血流动力学机制，3) 描述所涉及的神经和体液效应器机制，4) 确定局部血管床(内脏肌与骨骼肌) 电容响应以及这些响应涉及的机制，以及 5)确定刺激PVN对压力-直径的影响 内脏肌和骨骼肌中各静脉的相互关系 血管床。 这些目标将通过测量动脉和静脉血压来实现， 心输出量和区域血流量。在清醒的大鼠中，MCFP将是 用作静脉张力的指标，将从动脉计算 心输出量短暂中断后的静脉压。 将构建MCFP-血容量曲线来分析全身 压力-体积关系。MCFP将在激活过程中确定 手术前后室旁核的变化(如肾上腺髓质切除术)和 药理学干预(例如，肾上腺素受体阻滞剂)。在……里面 体内恒流灌流血管床制剂将用于 测定局部静脉电容反应并测定 静脉电容效应的血流动力学机制 脑室旁核的激活。最后，直接测量微静脉压。 和直径将使用伺服零压力测量 并在活体显微镜下评估PVN刺激对血管内皮细胞的影响。 单个静脉中的压力-容量关系。 拟议的研究使用了多方面的方法来系统地 室旁核在静脉电容控制中的作用研究 在三个层次的血管组织中。这些研究将提供 关于中枢神经系统控制静脉功能的有意义的新信息。 由于静脉功能改变，这种信息在临床上是相关的。 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(如可乐定)可能会影响静脉容量。此外, 静脉系统参与心血管对压力的反应， 然而，涉及中枢神经系统的部位和机制仍有待阐明。 建议的研究将为未来提供重要的背景数据。 旨在解决这些问题的研究。

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.