Cystathionine-β-Synthase Gene Transfer Into Rostral Ventrolateral Medulla Exacerbates Hypertension via Nitric Oxide in Spontaneously Hypertensive Rats
Cystathionine-β-Synthase Gene Transfer Into Rostral Ventrolateral Medulla Exacerbates Hypertension via Nitric Oxide in Spontaneously Hypertensive Rats
复制标题
DOI：
10.1093/ajh/hpu299
复制
发表时间：
2015-09-01
影响因子：
3.2
通讯作者：
Wu, Yu-Ming
中科院分区：
文献类型：
--
作者：
Duan, Xiao-Cui;Liu, Shang-Yu;Wu, Yu-Ming
延髓头端腹外侧区（RVLM）在心血管功能的中枢调节中起着至关重要的作用。胱硫醚-β-合酶（CBS）是一种主要的硫化氢（H2S）生成酶，主要在大脑中被鉴定。本研究旨在检测CBS在自发性高血压大鼠（SHR）RVLM中的表达，并探讨其调节交感神经流出和血压（BP）的作用和机制。越来越多的证据表明，H2S与一氧化氮（NO）相互作用调节心血管功能。因此，我们推测CBS在RVLM中表达的减少可能参与了L-arginine/NO通路的紊乱，其随后影响SHR的BP。CBS在RVLM的过度表达引起血压，心率和尿去甲肾上腺素排泄的SHR，但不是在WKY显着增加。在基因转移后第7天进行急性实验。CBS基因转染后SHR的NO代谢产物水平、神经元型NO合成酶和γ-氨基丁酸水平均降低。此外，与转染AdEGFP的SHR相比，转染AdCBS的SHR对RVLM内微量注射NG-单甲基-L-精氨酸的升压反应减弱。结论在RVLM内过表达CBS可增强SHR的升压反应，但在WKY中无此作用，NO系统参与了此作用。结果表明，H2S信号在大脑中的改变可能与高血压的发展。
BACKGROUNDRostral ventrolateral medulla (RVLM) plays a crucial role in the central regulation of cardiovascular functions. Cystathionine-beta-synthase (CBS) is a major hydrogen sulfide (H2S)-generating enzyme that has been identified mainly in the brain. The present study was designed to examine CBS expression and determine its roles and mechanisms of regulating sympathetic outflow and blood pressure (BP) in the RVLM in spontaneously hypertensive rats (SHR).METHODS AND RESULTSCBS expression was decreased in the RVLM in SHR compared to Wistar-Kyoto (WKY) rats. Accumulating evidences suggest that H2S interacts with nitric oxide (NO) to regulate cardiovascular function. Therefore, we hypothesize that the decrease in CBS expression in the RVLM may be involved in the disorder of L-arginine/NO pathway, which subsequently affects BP in SHR. Overexpression of CBS in the RVLM caused significant increases in BP, heart rate, and urinary norepinephrine excretion in SHR but not in WKY. Acute experiments were carried out at day 7 after gene transfer. NO metabolite levels, neuronal NO synthase, and gamma-amino butyric acid were decreased in SHR after CBS gene transfer. Furthermore, pressor responses to microinjection of NG-monomethyl-L-arginine into RVLM were blunt in SHR transfected with AdCBS compared to SHR transfected with AdEGFP.CONCLUSIONSOverexpression of CBS in the RVLM elicits enhanced pressor responses in SHR, but not in WKY, and the NO system is involved in these effects. The results suggest that alterations of H2S signaling in the brain may be associated with the development of hypertension.