University Center for Biomedical Research, Universidad de Colima, Ave. 25 de Julio s/n, Colima 28045, Mexico.
Nitric Oxide. 2010 May 15;22(4):296-303. doi: 10.1016/j.niox.2010.02.003. Epub 2010 Feb 13.
Neuronal nitric oxide synthase (nNOS), which catalyzes the generation of nitric oxide (NO), is expressed by neuron subpopulations in the CNS. Nitric oxide is involved in neurotransmission and central glucose homeostasis. Our prior studies have shown that carotid body receptors participate in brain glucose regulation in vivo, and suggest the presence of a NO tonic mechanism in the solitary tract nucleus (STn). However, the role of NO within STn in glucose control remains unknown. In this study, we explored the potential regulatory role of NO on brain glucose retention induced by carotid body chemoreceptor anoxic stimulation with sodium cyanide (NaCN) which inhibits oxidative metabolism. Intracisternal infusions of nitroxidergic drugs before carotid chemoreceptor stimulation in anesthetized rats, elicited changes in nitrite concentration in plasma and hypothalamus-pituitary (H-P) tissue, as well as in gene expression of neuronal and inducible isoforms (nNOS and iNOS) in H-P tissue. The changes observed in above variables modified brain glucose retention in an opposite direction. When the NO donor, sodium nitroprusside (SNP), was given before carotid stimulation, nitrite concentration in plasma and H-P tissue, and gene expression of nNOS and iNOS in H-P tissue increased, whereas brain glucose retention decreased. In contrast, when the NOS inhibitor, Nomega-nitro-L-arginine methyl ester (L-NAME) was infused immediately before carotid chemoreceptor stimulation, nitrite levels and nNOS expression decreased in plasma and H-P tissue, whereas brain glucose retention increased. Anoxic stimulation by itself induced an increase in the expression of both genes studied. All these results indicate that de novo expression of the nNOS gene in H-P tissue may be critically involved in central glucose changes observed after anoxic carotid chemoreceptor stimulation in conjunction with NO.
神经元型一氧化氮合酶（nNOS）催化一氧化氮（NO）的生成，由中枢神经系统中的神经元亚群表达。NO 参与神经传递和中枢葡萄糖稳态。我们之前的研究表明，颈动脉体受体参与体内脑葡萄糖调节，并提示在孤束核（STn）中存在 NO 紧张机制。然而，NO 在 STn 内对葡萄糖控制的作用尚不清楚。在这项研究中，我们探讨了 NO 在前脑化学感受性缺氧刺激（用氰化钠抑制氧化代谢）引起的脑葡萄糖保留中的潜在调节作用。在麻醉大鼠中，在颈动脉化学感受器刺激前向蛛网膜下腔输注氮氧自由基药物，引起血浆和下丘脑-垂体（H-P）组织中硝酸盐浓度以及 H-P 组织中神经元和诱导型同工酶（nNOS 和 iNOS）的基因表达发生变化。上述变量的变化以相反的方向改变脑葡萄糖保留。当给予 NO 供体硝普钠（SNP）后刺激颈动脉时，血浆和 H-P 组织中的硝酸盐浓度以及 H-P 组织中的 nNOS 和 iNOS 基因表达增加，而脑葡萄糖保留减少。相反，当立即在颈动脉化学感受器刺激前输注 NOS 抑制剂 Nω-硝基-L-精氨酸甲酯（L-NAME）时，血浆和 H-P 组织中的硝酸盐水平和 nNOS 表达降低，而脑葡萄糖保留增加。单独缺氧刺激本身会诱导这两个研究基因的表达增加。所有这些结果表明，H-P 组织中 nNOS 基因的新表达可能与 NO 一起参与缺氧颈动脉化学感受器刺激后观察到的中枢葡萄糖变化。
