Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, Nebraska 68198-5850, USA.
Am J Physiol Heart Circ Physiol. 2012 Apr 15;302(8):H1700-11. doi: 10.1152/ajpheart.00722.2011. Epub 2012 Feb 3.
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.
先前的研究表明，慢性心力衰竭（CHF）大鼠的室旁核（PVN）活性增加；然而，PVN 中的自主前神经元是否过度活跃尚不清楚。此外，尚不清楚这些神经元对压力感受器或渗透挑战的反应是否发生改变。实验在冠状动脉结扎后 6-8 周的 CHF 大鼠中进行。记录 PVN 中的自发性活动神经元，其中 36%可从延髓腹外侧头端（RVLM）逆行激活。与假手术（sham）大鼠相比，CHF 大鼠的 RVLM 投射到 PVN（PVN-RVLM）神经元的基线放电率明显更高（6.0±0.6 与 2.6±0.3 个/秒，P<0.05）。在 CHF 大鼠中，微量注射 N-甲基-D-天冬氨酸（NMDA）受体拮抗剂 D,L-2-氨基-5-磷戊酸（D,L-2-amino-5-phosphonovaleric acid）可使 PVN-RVLM 神经元的基础放电减少 80%，而在 sham 大鼠中减少 37%。52%的自发性活动 PVN-RVLM 神经元对平均动脉压（MAP）的变化有反应。MAP 降低后（+52±7%与+184±61%）或 MAP 升高后（-42±8%与-71±6%），PVN-RVLM 神经元放电率的变化在 CHF 大鼠中明显减弱，与 sham 大鼠相比。大多数 PVN-RVLM 神经元（63%），包括所有压力感受性 PVN-RVLM 神经元，对内颈动脉注射高渗 NaCl（2.1 渗透压）兴奋，而一小部分（7%）被抑制。与 sham 大鼠相比，CHF 大鼠对高渗刺激的 PVN-RVLM 神经元放电率增加明显增强（134±15%与 92±13%）。综上所述，这些数据表明，PVN-RVLM 神经元在基础条件下更活跃，这种过度兴奋是由 CHF 大鼠中增强的谷氨酸能张力介导的。此外，这种增强的 PVN-RVLM 神经元的激活可能导致 CHF 期间观察到的压力感受器和渗透挑战反应改变。
