Ishide Takeshi, Preuss Charles V, Maher Timothy J, Ally Ahmmed
Department of Cardiovascular Science and Medicine, Chiba University, School of Medicine, Chiba 260, Japan.
Neurosci Res. 2005 May;52(1):21-30. doi: 10.1016/j.neures.2005.01.002. Epub 2005 Jan 26.
Nitric oxide synthase (NOS), necessary for the production of nitric oxide from l-arginine, exists in three isoforms: neuronal NOS (nNOS), endothelial NOS (eNOS), and inducible NOS (iNOS). We have previously demonstrated that blockade of nNOS within the rostral (RVLM) and caudal ventrolateral medulla (CVLM) differentially modulated cardiovascular responses to static exercise [Ishide, T., Nauli, S.M., Maher, T.J., Ally, A., 2003. Cardiovascular responses and neurotransmitter changes following blockade of nNOS within the ventrolateral medulla during static muscle contraction. Brain Res. 977, 80-89]. In this study, we have examined the effects of bilaterally microdialyzing a specific eNOS antagonist into the RVLM and CVLM on cardiovascular responses and glutamatergic/GABAergic neurotransmission during the exercise pressor reflex in anesthetized rats. Bilateral microdialysis of a selective eNOS antagonist, l-N(5)-(1-iminoethyl)ornithine (l-NIO; 10.0 microM) into the RVLM potentiated cardiovascular responses and increased extracellular fluid glutamate levels during a static muscle contraction. At the same time, levels of GABA within the RVLM were decreased. The cardiovascular responses and neurochemical changes to muscle contraction recovered after discontinuation of the drug. In contrast, bilateral application of the eNOS antagonist into the CVLM attenuated cardiovascular responses and glutamate concentrations during a static muscle contraction, but augmented levels of GABA. These results demonstrate that eNOS within the ventrolateral medulla plays an important role in modulating glutamate/GABAergic neurotransmission, that in turn regulates the exercise pressor reflex. The present study provides further evidence of simultaneous sympathoexcitatory and sympathoinhibitory effects of nitric oxide within the RVLM and CVLM involved in the neural control of circulation during static exercise.
一氧化氮合酶（NOS）是从L-精氨酸产生一氧化氮所必需的，它有三种同工型：神经元型一氧化氮合酶（nNOS）、内皮型一氧化氮合酶（eNOS）和诱导型一氧化氮合酶（iNOS）。我们之前已经证明，阻断延髓头端腹外侧区（RVLM）和尾端腹外侧延髓（CVLM）内的nNOS会对静态运动的心血管反应产生不同的调节作用[石出，T.，瑙利，S.M.，马赫，T.J.，艾利，A.，2003年。静态肌肉收缩期间延髓腹外侧区nNOS被阻断后心血管反应和神经递质变化。《脑研究》977，80 - 89]。在本研究中，我们研究了在麻醉大鼠的运动升压反射过程中，将一种特异性eNOS拮抗剂双侧微量透析到RVLM和CVLM中对心血管反应以及谷氨酸能/γ-氨基丁酸能神经传递的影响。将选择性eNOS拮抗剂L-N(5)-(1-亚氨基乙基)鸟氨酸（L-NIO；10.0微摩尔）双侧微量透析到RVLM中，在静态肌肉收缩期间增强了心血管反应，并增加了细胞外液谷氨酸水平。同时，RVLM内的γ-氨基丁酸水平降低。停药后，对肌肉收缩的心血管反应和神经化学变化恢复。相比之下，将eNOS拮抗剂双侧应用于CVLM，在静态肌肉收缩期间减弱了心血管反应和谷氨酸浓度，但增加了γ-氨基丁酸水平。这些结果表明，延髓腹外侧区的eNOS在调节谷氨酸能/γ-氨基丁酸能神经传递中起重要作用，而这反过来又调节运动升压反射。本研究进一步证明了RVLM和CVLM内的一氧化氮在静态运动期间参与循环神经控制时具有同时的交感兴奋和交感抑制作用。
