title: Cystathionine-β-Synthase Gene Transfer Into Rostral Ventrolateral Medulla Exacerbates Hypertension via Nitric Oxide in Spontaneously Hypertensive Rats.
abstract: BACKGROUND
  Rostral ventrolateral medulla (RVLM) plays a crucial role in the central regulation of cardiovascular functions. Cystathionine-β-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).
  
  
  RESULTS
  CBS 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 γ-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.
  
  
  CONCLUSIONS
  Overexpression 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.
authors: Department of Physiology, Institute of Basic Medicine, Hebei Medical University, Shijiazhuang, China; Hebei Key Lab of Laboratory Animal Science, Department of Laboratory Animal Science, Hebei Medical University, Shijiazhuang, China;
authors: Xiao-Cui
authors: XC
authors: Duan
authors: Department of Physiology, Institute of Basic Medicine, Hebei Medical University, Shijiazhuang, China;
authors: Shang-Yu
authors: SY
authors: Liu
authors: Department of Education Administration, Third Hospital of Hebei Medical University, Shijiazhuang, China.
authors: Rong
authors: R
authors: Guo
authors: Department of Physiology, Institute of Basic Medicine, Hebei Medical University, Shijiazhuang, China;
authors: Lin
authors: L
authors: Xiao
authors: Department of Physiology, Institute of Basic Medicine, Hebei Medical University, Shijiazhuang, China;
authors: Hong-Mei
authors: HM
authors: Xue
authors: Department of Physiology, Institute of Basic Medicine, Hebei Medical University, Shijiazhuang, China;
authors: Qi
authors: Q
authors: Guo
authors: Department of Physiology, Institute of Basic Medicine, Hebei Medical University, Shijiazhuang, China;
authors: Sheng
authors: S
authors: Jin
authors: Department of Physiology, Institute of Basic Medicine, Hebei Medical University, Shijiazhuang, China; wuyum@yahoo.com.
authors: Yu-Ming
authors: YM
authors: Wu
mesh_terms: D000818:Animals; D001794:Blood Pressure; D003541:Cystathionine beta-Synthase / Q000096:biosynthesis* / Q000235:genetics; D004195:Disease Models, Animal; D004790:Enzyme Induction; D006339:Heart Rate; D006862:Hydrogen Sulfide / Q000378:metabolism; D006973:Hypertension / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology; D008297:Male; D008526:Medulla Oblongata / Q000201:enzymology* / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D009638:Norepinephrine / Q000652:urine; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D015398:Signal Transduction; D013564:Sympathetic Nervous System / Q000378:metabolism / Q000503:physiopathology; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D009569:Nitric Oxide; D005680:gamma-Aminobutyric Acid; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D003541:Cystathionine beta-Synthase; D009638:Norepinephrine; D006862:Hydrogen Sulfide
keywords: blood pressure; cystathionine-β-synthase; hydrogen sulfide; hypertension; nitric oxide; overexpression; rostral ventrolateral medulla.