NG-methyl-L-arginine, an inhibitor of L-arginine-derived nitric oxide synthesis, stimulates renal sympathetic nerve activity in vivo. A role for nitric oxide in the central regulation of sympathetic tone?

NG-methyl-L-arginine, an inhibitor of L-arginine-derived nitric oxide synthesis, stimulates renal sympathetic nerve activity in vivo. A role for nitric oxide in the central regulation of sympathetic tone?
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DOI:
10.1161/01.res.70.3.607
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发表时间:
1992-03
影响因子:
20.1
通讯作者:
I. Sakuma;H. Togashi;M. Yoshioka;Hideya Saito-;M. Yanagida;M. Tamura;Takeshi Kobayashi;H. Yasuda
I. Sakuma;H. Togashi;M. Yoshioka;Hideya Saito-;M. Yanagida;M. Tamura;Takeshi Kobayashi;H. Yasuda
中科院分区:
医学1区
文献类型:
--
作者:
I. Sakuma;H. Togashi;M. Yoshioka;Hideya Saito-;M. Yanagida;M. Tamura;Takeshi Kobayashi;H. Yasuda

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外周血管内皮源性一氧化氮(NO)的持续产生可调节血管阻力和血压。当谷氨酸受体激活时,大脑中也会形成一氧化氮,谷氨酸受体被认为是介导中枢自主神经反射的媒介。在本研究中,我们评估了NO是否在中枢自主神经调节中发挥作用。为此,我们观察了由L精氨酸合成NO的选择性阻断剂NG-甲基-L-精氨酸对麻醉大鼠肾交感神经活动、血压和心率的影响。NMA可引起剂量依赖性的血压持续升高(分别在10和50mumol/kg静脉注射后5分钟,约20和30毫米汞柱)。心率和核糖核酸一过性降低(分别为每分钟15次和40%);核糖核酸随后增加(100%),而血压保持升高。压力感受器去传入显著改变对NMA的这些反应;心率和RNA的一过性降低被消除,而RNA和血压的升高被显著增强。脊髓C-1-C-2切断后,RNA无明显增加,血压升高幅度较小。L-精氨酸可阻断N-甲基-天冬氨酸引起的血压和核糖核酸的升高。因此,除了通过外周作用调节血管阻力外,NO还可能在交感神经张力的中枢调节中发挥作用。
Continuous production of endothelium-derived nitric oxide (NO) in peripheral vessels has been shown to modulate vascular resistance and blood pressure. NO is also formed in the brain upon activation of glutamate receptors, which are thought to mediate central autonomic reflexes. In the present study we assessed whether NO plays a role in central autonomic regulation. For this, we have investigated the effects of NG-methyl-L-arginine (NMA), a selective inhibitor of NO synthesis from L-arginine, on sympathetic renal nerve activity (RNA), blood pressure, and heart rate in the anesthetized rat. NMA elicited a dose-dependent sustained increase in blood pressure (approximately 20 and 30 mm Hg, 5 minutes after 10 and 50 mumol/kg i.v., respectively). Heart rate and RNA decreased transiently (15 beats per minute and 40%, respectively); RNA subsequently increased (100%) while blood pressure remained elevated. Baroreceptor deafferentation markedly altered these responses to NMA; the transient decreases in heart rate and RNA were abolished, whereas the increases in RNA and blood pressure were significantly potentiated. After spinal C-1-C-2 transection, there was no increase in RNA, and blood pressure increased to a smaller extent. L-Arginine blocked the NMA-induced increases in blood pressure and RNA. Thus, in addition to modulating vascular resistance by a peripheral action, NO may also play a role in the central regulation of sympathetic tone.