EXERCISE AND SYMPATHETIC NERVE ACTIVITY IN HEART FAILURE

慢性心力衰竭（CHF）状态下交感神经活动的调节是一个复杂且至关重要的问题。在过去的20年里，该实验室一直在研究CHF动物模型中心血管功能的异常神经体液控制机制。 我们已经清楚地表明，增强交感神经流出，这是CHF状态的特征，是一个多因素的过程，涉及缓冲反射和交感神经流出的中枢调制的改变。 运动调节已被证明可以减少CHF状态的许多症状。 运动调节对CHF状态有益的机制在很大程度上是未知的。本实验室的初步证据表明，CHF运动条件反射不仅可以逆转交感神经兴奋状态，而且可以上调脑中nNOS mRNA和蛋白。由于一氧化氮已被证明是交感神经功能的调节剂，我们假设运动调节减少CHF交感神经流出的一种机制是通过中枢上调中枢神经系统区域中的nNOS，该区域关键参与交感神经流出的调节。 因此，我们将确定运动调节对静息肾交感神经活动（RSNA）和RSNA的压力反射控制的作用，以及确定运动调节对清醒的、慢性仪器化的有和无起搏诱导的CHF的兔的nNOS和mRNA和蛋白质的中枢表达的影响。 此外，运动可能会减少中枢血管紧张素II对交感神经流出的作用。 因此，本建议的另一个目的是确定中枢血管紧张素II的作用及其与一氧化氮的相互作用，在兔CHF。 这些研究将提供新的和独特的信息，在CHF状态下的交感神经流出的调节运动的作用。

The regulation of sympathetic nerve activity in the chronic heart failure (CHF) state is a complex and critically important issue. Over the past 20 years this laboratory has been investigating mechanisms of abnormal neuro-humoral control of cardiovascular function in animal models of CHF. We have clearly shown that enhanced sympathetic outflow, which is characteristic of the CHF state, is a multi-factorial process involving alterations in both buffer reflexes and in the central modulation of sympathetic outflow. Exercise conditioning has been shown to reduce many of the symptoms of the CHF state. The mechanisms by which exercise conditioning is beneficial in the CHF state are largely unknown. Preliminary evidence from this laboratory suggests that exercise conditioning in CHF can not only reverse the sympatho-excitatory state but can up regulate nNOS mRNA and protein in the brain. Because nitric oxide has been shown to be a modulator of sympathetic function we hypothesize that one mechanism by which exercise conditioning reduces sympathetic outflow in CHF is by a central up regulation of nNOS in areas of the central nervous system which are critically involved in the regulation of sympathetic outflow. Therefore, we will determine the role of exercise conditioning on resting renal sympathetic nerve activity (RSNA) and on baroreflex control of RSNA as well as determining the effects of exercise conditioning on the central expression of nNOS and mRNA and protein in conscious, chronically instrumented rabbits with and without pacing-induced CHF. In addition, exercise may reduce the role of central angiotensin II on sympathetic outflow. Therefore, an additional aim of this proposal is to determine the role of central angiotensin II and its interaction with nitric oxide in rabbits with CHF. These studies will provide new and unique information on the role of exercise in the regulation of sympathetic outflow in the CHF state.