FUNCTION OF THE PVN IN HEART FAILURE--ROLE OF NITRIC OXIDE AND GABA

心力衰竭（HF）患者和所有HF动物模型均表现出交感神经激活增加。 这种异常增加了HF期间的死亡风险。 这些异常背后的中枢机制知之甚少。 我们最近获得的数据表明，室旁核（PVN），一个中央坐已知从心脏接收传入信息，并改变交感神经流出，可能有助于在HF状态期间的神经体液驱动的升高。此外，改变一氧化氮（NO）和γ-氨基丁酸（GABA）的PVN内的机制可能参与这种交感神经兴奋。 这一提议提出了一个假设，即PVN内的NO和GABA机制被破坏有助于心力衰竭中交感神经驱动的增加。 我们建议：第一，确定PVN内的NO机制是否有助于HF大鼠交感神经活性的增加;第二，确定PVN内的GABA机制是否有助于HF大鼠交感神经活性的增加;第三，确定HF大鼠PVN内的NO和GABA机制的相互作用是否改变;第四，确定运动训练是否改善HF大鼠PVN内改变的NO和GABA机制。 预计PVN内的NO和GABA机制有助于HF期间通常观察到的交感神经激活。 结果应提供重要的新信息，交感神经兴奋，特别是参与的NO和GABA系统内的PVN，在增加交感神经激活NF状态的中央机制。 了解迄今为止尚未研究的中枢机制在HF状态下交感神经激活增加中的作用。 了解中枢机制的作用，没有研究到目前为止，在增加交感神经驱动将提高我们的能力，治疗HF条件及其心血管并发症。

Patients with heart failure (HF) and all animal models of HF exhibit an increased sympathetic neural activation. This abnormality increases the risk of mortality during HF. The central mechanisms which underlie these abnormalities are poorly understood. We have recently obtained data which suggests that the paraventricular nucleus (PVN), a central sit known to receive afferent information from the heart and to alter sympathetic outflow, may contribute to the elevated neuro-humoral drive during the HF state. Furthermore, altered nitric oxide (NO) and gamma-amino butyric acid (GABA) mechanisms within the PVN may be involved in this sympatho-excitation. This proposal sets the hypothesis that disrupted NO and GABA mechanisms within the PVN contribute to the increased sympathetic drive in heart failure. We propose to: first, determine if No mechanisms within the PVN contribute to the increased sympathetic nerve activity in rats with HF; second, determine if GABA mechanisms within the PVN contribute to the increased sympathetic nerve activity in rats with HF; third, determine if there is altered interaction of NO and GABA mechanisms within the PVN in rats with HF; and fourth, determine if exercise training improves the altered NO and GABA mechanisms within the PVN in rats with HF. It is anticipated that No and GABA mechanisms within the PVN contribute to the sympathetic neural activation commonly observed during HF. The results should provide significant new information regarding central mechanisms of sympatho-excitation, specifically involvement of the NO and GABA systems within the PVN, in the increased sympathetic neural activation in the NF state. Understanding the role of central mechanisms not studied to date, in the increased sympathetic neural activation in the HF state. Understanding the role of central mechanisms, not studied to date, in the increased sympathetic neural drive would enhance our ability to treat HF condition and its cardiovascular complications.