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

心力衰竭患者和所有心力衰竭动物模型都表现出交感神经激活增加。这种异常增加了心力衰竭期间死亡的风险。人们对这些异常的核心机制知之甚少。我们最近获得的数据表明，室旁核(PVN)，一个已知从心脏接受传入信息并改变交感神经流出的中枢部位，可能在HF状态下参与神经-体液驱动的升高。此外，PVN内改变的一氧化氮(NO)和γ-氨基丁酸(GABA)机制可能参与了这种交感兴奋。这一建议提出了一个假设，即破坏PVN内的NO和GABA机制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机制是否有助于心衰大鼠交感神经活性的增加；第二，确定PVN内的GABA机制是否有助于心衰大鼠交感神经活动的增加；第三，确定心衰大鼠室旁核内NO和GABA机制的相互作用是否发生改变；第四，确定运动训练是否改善了心衰大鼠室旁核内改变的NO和GABA机制。可以预见，室旁核内的NO和GABA机制有助于在心力衰竭时观察到交感神经的激活。这些结果将为交感神经兴奋的中枢机制提供重要的新信息，特别是参与PVN内的NO和GABA系统参与交感神经在NF状态下的激活。了解目前尚未研究的中枢机制在心力衰竭状态交感神经激活增加中的作用。了解中枢机制在交感神经驱动增加中的作用将增强我们治疗心力衰竭及其心血管并发症的能力。

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.