Ally Ahmmed, Phattanarudee Siripan, Kabadi Shruti, Patel Maitreyee, Maher Timothy J
Department of Pharmaceutical Sciences, Lloyd L. Gregory School of Pharmacy, Palm Beach Atlantic University, West Palm Beach, FL 33416, USA.
Brain Res. 2006 May 23;1090(1):123-33. doi: 10.1016/j.brainres.2006.03.054. Epub 2006 May 2.
The enzyme nitric oxide synthase (NOS) which is necessary for the production of nitric oxide from L-arginine exists in three isoforms: neuronal NOS (nNOS), endothelial NOS (eNOS), and inducible NOS (iNOS). Our previous studies have demonstrated the roles of nNOS and eNOS within the rostral (RVLM) and caudal ventrolateral medulla (CVLM) in modulating cardiovascular responses during static skeletal muscle contraction via altering localized glutamate and GABA levels (Brain Res. 977 (2003) 80-89; Neuroscience Res. 52 (2005) 21-30). In this study, we investigated the role of iNOS within the RVLM and CVLM on cardiovascular responses and glutamatergic/GABAergic neurotransmission during the exercise pressor reflex. Bilateral microdialysis of a selective iNOS antagonist, aminoguanidine (AGN; 1.0 microM), for 60 min into the RVLM attenuated increases in mean arterial pressure (MAP), heart rate (HR), and extracellular glutamate levels during a static muscle contraction. Levels of GABA within the RVLM were increased. After 120 min of discontinuation of the drug, MAP and HR responses and glutamate/GABA concentrations recovered to baseline values during a subsequent muscle contraction. In contrast, bilateral application of AGN (1.0 microM) into CVLM potentiated cardiovascular responses and glutamate concentration while attenuating levels of GABA during a static muscle contraction. All values recovered after 120 min of discontinuation of the drug. These results demonstrate that iNOS within the ventrolateral medulla plays an important role in modulating cardiovascular responses and glutamatergic/GABAergic neurotransmission that regulates the exercise pressor reflex.
一氧化氮合酶（NOS）是从L-精氨酸生成一氧化氮所必需的酶，它以三种同工型存在：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）。我们之前的研究已经证明，nNOS和eNOS在延髓头端腹外侧区（RVLM）和尾端腹外侧延髓（CVLM）中，通过改变局部谷氨酸和γ-氨基丁酸水平，在静态骨骼肌收缩期间调节心血管反应（《脑研究》977（2003）80 - 89；《神经科学研究》52（2005）21 - 30）。在本研究中，我们研究了RVLM和CVLM中的iNOS在运动升压反射期间对心血管反应以及谷氨酸能/γ-氨基丁酸能神经传递的作用。将选择性iNOS拮抗剂氨基胍（AGN；1.0微摩尔）双侧微透析60分钟至RVLM，可减弱静态肌肉收缩期间平均动脉压（MAP）、心率（HR）和细胞外谷氨酸水平的升高。RVLM内的γ-氨基丁酸水平升高。停药120分钟后，在随后的肌肉收缩期间，MAP和HR反应以及谷氨酸/γ-氨基丁酸浓度恢复到基线值。相比之下，将AGN（1.0微摩尔）双侧应用于CVLM可增强心血管反应和谷氨酸浓度，同时减弱静态肌肉收缩期间的γ-氨基丁酸水平。停药120分钟后所有值均恢复。这些结果表明，腹外侧延髓中的iNOS在调节心血管反应以及调节运动升压反射的谷氨酸能/γ-氨基丁酸能神经传递中起重要作用。
