Blood pressure control by caudal ventrolaeral medulla

描述（由申请人提供）：大脑在通过自主神经系统调节动脉压（AP）中起重要作用。申请人的长期目标是了解中枢神经系统（CNS）如何在正常AP的条件下控制交感神经血管紧张度以及高血压如何改变该功能。许多形式的高血压与交感神经活动（SNA）升高有关，尽管这种交感神经激活的基础还不清楚。正常情况下，SNA受到尾侧延髓腹外侧区（CVLM）中GABA能神经元的抑制，以维持一致的AP。对于SNA和AP的短期控制，这些GABA能CVLM神经元是压力感受器反射的中枢通路中的重要环节。然而，GABA能CVLM神经元对于独立于压力感受器反射设置SNA的长期水平也明显重要。我们已经观察到，在慢性缺乏压力感受器输入或其在孤束核（NTS）的终止位点，恢复正常的平均AP与正常的CVL M介导的抑制SNA和AP。相反，自发性高血压大鼠SNA升高，这可能与CVLM介导的SNA和AP抑制受损有关。除了压力感受器输入和NTS，很少有人知道的中枢机制，这些强大的GABA能CVLM神经元的活动调节。该项目将使用大鼠最先进的方法（即电生理学，神经解剖学和分子方法）的组合来确定在正常血压和高血压条件下大脑的其他区域如何调节GABA能CVLM神经元的活性。具体来说，我们将确定是否确定的CVLM从下丘脑室旁核和中脑导水管周围灰质腹外侧的GABA能输入激活CVLM神经元，项目的头端腹外侧延髓（RVLM）。我们将使用慢性动脉压力感受器去神经大鼠作为血压正常的模型，以检查可能被强大的压力感受器输入所掩盖的GABA能CVLM神经元的输入。此外，我们将确定是否CVLM介导的抑制SNA在自发性高血压大鼠受损。总的来说，这些研究将提供一个复杂的分析机制的脑干的作用，在长期的调节交感神经血管紧张素和AP，并将确定功能的变化，发生与慢性压力感受器去神经和自发性高血压。

DESCRIPTION (provided by applicant): The brain plays an important role in the regulation of arterial pressure (AP) via the autonomic nervous system. The long range goal of the applicant is to understand how the central nervous system (CNS) controls sympathetic vasomotor tone under conditions of normal AP and how the function is altered with hypertension. Many forms of hypertension are linked with elevated sympathetic nerve activity (SNA), although the basis of this sympatho-activation is not well understood. Normally, SNA is restrained by GABAergic neurons in the caudal ventrolateral medulla (CVLM) to maintain a consistent AP. For the short-term control of SNA and AP, these GABAergic CVLM neurons are an essential link in the central pathway for the baroreceptor reflex. However, GABAergic CVLM neurons also are clearly important for setting the long-term level of SNA independent of the baroreflex. We have observed that in the chronic absence of baroreceptor inputs or their site of termination in the nucleus tractus solitarius (NTS), the restoration of a normal mean AP is associated with a normal CVLM-mediated inhibition of SNA and AP. In contrast, spontaneously hypertensive rats have elevated SNA which may be linked with impaired CVLM-mediated inhibition of SNA and AP. Apart from baroreceptor inputs and the NTS, little is known about the central mechanisms regulating the activity of these powerful GABAergic CVLM neurons. This project will use a combination of state-of-the-art methods in rats (i.e. electrophysiological, neuroanatomical, and molecular approaches) to determine how other areas of the brain regulate the activity of GABAergic CVLM neurons under normotensive and hypertensive conditions. Specifically, we will determine whether identified glutamatergic inputs to the CVLM from the paraventricular nucleus of the hypothalamus and ventrolateral periaqueductal gray activate GABAergic CVLM neurons that project to the rostral ventrolateral medulla (RVLM). We will use chronic arterial baroreceptor denervated rats as a normotensive model to examine inputs to GABAergic CVLM neurons that may be masked by powerful baroreceptor inputs. In addition, we will determine whether the CVLM-mediated inhibition of SNA is impaired in spontaneously hypertensive rats. Collectively, these studies will provide a sophisticated analysis of the mechanisms underlying the brainstem's role in the long-term regulation of sympathetic vasomotor tone and AP and will determine functional changes that occur with chronic baroreceptor denervation and spontaneous hypertension.