Enhanced activation of RVLM-projecting PVN neurons in rats with chronic heart failure
Enhanced activation of RVLM-projecting PVN neurons in rats with chronic heart failure
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DOI：
10.1152/ajpheart.00722.2011
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发表时间：
2012-04-01
影响因子：
4.8
通讯作者：
Patel, Kaushik P.
中科院分区：
文献类型：
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作者：
Xu, Bo;Zheng, Hong;Patel, Kaushik P.
徐B，郑H，Patel KP.慢性心力衰竭大鼠RVLM投射PVN神经元的激活增强Am J Physiol Heart Circ Physiol 302：H1700-H1711，2012。首次发表于2012年2月3日; doi：10.1152/ajpheart.00722.2011。以往的研究表明，有增加室旁核（PVN）在慢性心力衰竭（CHF）大鼠的激活，但是，目前尚不清楚，如果PVN内的前自主神经元是特别过度活跃。此外，尚不清楚这些神经元是否对压力感受器或渗透压挑战有改变的反应。实验在CHF大鼠（冠状动脉结扎后6-8周）中进行。在PVN中记录到自发活动神经元，其中36%是从延髓头端腹外侧（RVLM）逆向激活的。CHF大鼠PVN-RVLM投射神经元的基线放电率显著高于假手术大鼠（6.0 +/- 0.6 vs. 2.6 +/- 0.3 spikes/s，P < 0.05）。皮可注射N-甲基-D-天冬氨酸（NMDA）受体拮抗剂D，L-2-氨基-5-膦酰基戊酸（D，L-2-amino-5-phosphonovaleric acid）使CHF大鼠PVN-RVLM神经元的基础放电显著减少80%，而假手术大鼠为37%。52%的自发活动PVN-RVLM神经元对平均动脉压（MAP）的变化有反应。与假手术大鼠相比，CHF大鼠MAP降低（+52 +/- 7% vs. +184 +/- 61%）或MAP升高（-42 +/- 8% vs. -71 +/- 6%）后PVN-RVLM神经元放电率的变化显著减弱。大多数PVN-RVLM神经元（63%），包括所有的压力敏感性PVN-RVLM神经元，兴奋的颈内动脉注射高渗NaCl（2.1 μ l/l），而一小部分（7%）被抑制。与假手术大鼠相比，CHF大鼠PVN-RVLM神经元对高渗刺激的放电率增加显著增强（134 +/- 15% vs. 92 +/- 13%）。两者合计，这些数据表明，PVN-RVLM神经元在基础条件下更活跃，这种过度激活是由CHF大鼠中增强的多巴胺能神经元介导的。此外，这种增强的PVN-RVLM神经元的激活可能有助于改变CHF期间观察到的压力感受器和渗透压挑战的反应。
Xu B, Zheng H, Patel KP. Enhanced activation of RVLM-projecting PVN neurons in rats with chronic heart failure. Am J Physiol Heart Circ Physiol 302: H1700-H1711, 2012. First published February 3, 2012; doi: 10.1152/ajpheart.00722.2011.-Previous studies have indicated that there is increased activation of the paraventricular nucleus (PVN) in rats with chronic heart failure (CHF); however, it is not clear if the preautonomic neurons within the PVN are specifically overactive. Also, it is not known if these neurons have altered responses to baroreceptor or osmotic challenges. Experiments were conducted in rats with CHF (6-8 wk after coronary artery ligation). Spontaneously active neurons were recorded in the PVN, of which 36% were antidromically activated from the rostral ventrolateral medulla (RVLM). The baseline discharge rate in RVLM-projecting PVN (PVN-RVLM) neurons from CHF rats was significantly greater than in sham-operated (sham) rats (6.0 +/- 0.6 vs. 2.6 +/- 0.3 spikes/s, P < 0.05). Picoinjection of the N-methyl-D-aspartate (NMDA) receptor antagonist D, L-2-amino-5-phosphonovaleric acid significantly decreased the basal discharge of PVN-RVLM neurons by 80% in CHF rats compared with 37% in sham rats. Fifty-two percent of spontaneously active PVN-RVLM neurons responded to changes in the mean arterial pressure (MAP). The changes in discharge rate in PVN-RVLM neurons after a reduction in MAP (+52 +/- 7% vs. +184 +/- 61%) or an increase in MAP (-42 +/- 8% vs. -71 +/- 6%) were significantly attenuated in rats with CHF compared with sham rats. Most PVN-RVLM neurons (63%), including all barosensitive PVN-RVLM neurons, were excited by an internal carotid artery injection of hypertonic NaCl (2.1 osmol/l), whereas a smaller number (7%) were inhibited. The increase in discharge rate in PVN-RVLM neurons to hypertonic stimulation was significantly enhanced in rats with CHF compared with sham rats (134 +/- 15% vs. 92 +/- 13%). Taken together, these data suggest that PVN-RVLM neurons are more active under basal conditions and this overactivation is mediated by an enhanced glutamatergic tone in rats with CHF. Furthermore, this enhanced activation of PVN-RVLM neurons may contribute to the altered responses to baroreceptor and osmotic challenges observed during CHF.