Florey Institute of Neuroscience and Mental Health, University of Melbourne, Victoria, Australia.
Auton Neurosci. 2013 Apr;175(1-2):76-84. doi: 10.1016/j.autneu.2012.10.017. Epub 2013 Jan 14.
Heart failure (HF) is a serious debilitating condition with poor survival rates and an increasing level of prevalence. The excessive sympatho-excitation that is a hallmark of heart failure has long-term effects that contribute to disease progression. The mechanisms causing the increase in renal sympathetic nerve activity (RSNA) have been extensively investigated in experimental models of heart failure, but there is less information on the factors causing the increase in cardiac SNA (CSNA). This review focuses on our recent investigations of the mechanisms driving the increased CSNA in an ovine rapid ventricular pacing model of HF. In conscious sheep with mild heart failure (ejection fraction 35-40%) the arterial baroreflex control of CSNA was normal. In contrast, the normal inhibition of CSNA with volume expansion was abolished in HF, indicating desensitisation of the cardiopulmonary mechano-reflex. Antagonism of central angiotensin AT1 receptors with losartan substantially reduced CSNA, demonstrating a critical role for the central renin-angiotensin system. Investigation of the role of the paraventricular nucleus of the hypothalamus (PVN), which plays a critical role in setting the increased RSNA in HF, demonstrated that the PVN did not maintain the increased CSNA in HF or the resting level of CSNA in normal animals. Furthermore, inhibition of the PVN in normal animals reversed the reduction in RSNA, but not CSNA, induced by volume expansion. These studies emphasise that the mechanisms controlling CSNA in the normal state, and causing the increase in HF, are different to those controlling sympathetic activity to the kidney.
心力衰竭（HF）是一种严重的使人虚弱的疾病，其存活率低，发病率不断上升。心力衰竭的标志性过度交感兴奋具有长期影响，会导致疾病进展。在心力衰竭的实验模型中，已经广泛研究了导致肾交感神经活动（RSNA）增加的机制，但对于导致心脏交感神经活动（CSNA）增加的因素知之甚少。这篇综述重点介绍了我们最近在 HF 绵羊快速心室起搏模型中对导致 CSNA 增加的机制的研究。在轻度心力衰竭（射血分数 35-40%）的清醒绵羊中，动脉压力反射对 CSNA 的控制是正常的。相比之下，HF 中容量扩张对 CSNA 的正常抑制作用被消除，表明心肺机械反射脱敏。用氯沙坦拮抗中枢血管紧张素 AT1 受体可显著降低 CSNA，表明中枢肾素-血管紧张素系统的关键作用。对下丘脑室旁核（PVN）的作用进行了研究，PVN 在 HF 中增加 RSNA 中起着关键作用，结果表明，PVN 并没有维持 HF 中的增加 CSNA 或正常动物中的 CSNA 静息水平。此外，在正常动物中抑制 PVN 可逆转容量扩张引起的 RSNA 减少，但不能逆转 CSNA 减少。这些研究强调，控制正常状态下 CSNA 的机制，以及导致 HF 中 CSNA 增加的机制，与控制肾脏交感神经活动的机制不同。
