Contribution of Central Nervous System Endothelial Nitric Oxide Synthase to Neurohumoral Activation in Heart Failure Rats
Contribution of Central Nervous System Endothelial Nitric Oxide Synthase to Neurohumoral Activation in Heart Failure Rats
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DOI：
10.1161/hypertensionaha.111.175810
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发表时间：
2011-09-01
期刊：
影响因子：
8.3
通讯作者：
Stern, Javier E.
中科院分区：
文献类型：
--
作者：
Biancardi, Vinicia C.;Son, Sook J.;Stern, Javier E.
神经体液激活是心力衰竭（HF）的标志，与HF患者的进展和死亡率相关。因此，阐明其确切的潜在机制至关重要。除了其经典的外周血管扩张作用外，气体NO是中枢神经系统控制循环的关键神经递质。虽然越来越多的证据支持钝化的NO功能的HF神经体液激活的贡献，确切的细胞来源，和NO合酶（NOS）亚型参与，仍然未知。在这里，我们使用了多学科的方法来研究的表达，细胞分布和功能相关的内皮NOS亚型在下丘脑室旁核在假手术和HF大鼠。我们的研究结果表明，室旁核（主要局限于星形胶质细胞），这有助于组成NO的生物利用度，以及紧张性抑制前交感神经元的活动和交感神经兴奋流出室旁核的内皮NOS的高表达。HF大鼠室旁核的内皮NOS表达和内皮NOS衍生的NO可用性降低，进而导致NO对神经元活动和交感神经兴奋性流出的抑制作用减弱。总之，我们的研究支持钝化中枢神经系统内皮NOS衍生的NO作为HF神经体液激活的病理生理机制。（高血压。2011;58：454-463.）.在线补充资料
Neurohumoral activation, a hallmark in heart failure (HF), is linked to the progression and mortality of HF patients. Thus, elucidating its precise underlying mechanisms is of critical importance. Other than its classic peripheral vasodilatory actions, the gas NO is a pivotal neurotransmitter in the central nervous system control of the circulation. While accumulating evidence supports a contribution of blunted NO function to neurohumoral activation in HF, the precise cellular sources, and NO synthase (NOS) isoforms involved, remain unknown. Here, we used a multidisciplinary approach to study the expression, cellular distribution, and functional relevance of the endothelial NOS isoform within the hypothalamic paraventricular nucleus in sham and HF rats. Our results show high expression of endothelial NOS in the paraventricular nucleus (mostly confined to astroglial cells), which contributes to constitutive NO bioavailability, as well as tonic inhibition of presympathetic neuronal activity and sympathoexcitatory outflow from the paraventricular nucleus. A diminished endothelial NOS expression and endothelial NOS-derived NO availability were found in the paraventricular nucleus of HF rats, resulting, in turn, in blunted NO inhibitory actions on neuronal activity and sympathoexcitatory outflow. Taken together, our study supports blunted central nervous system endothelial NOS-derived NO as a pathophysiological mechanism underlying neurohumoral activation in HF. (Hypertension. 2011;58: 454-463.) . Online Data Supplement