title: Tetrandrine, an antihypertensive alkaloid, improves the sleep state of spontaneously hypertensive rats (SHRs).
abstract: BACKGROUND
  Radix of Stephania tetrandrae S. Moore has been used since antiquity in China as an antirheumatic, antihypertension, analgesic and antipyretic agent. Tetrandrine is the major component of Stephania tetrandrae. This study aims to evaluate the antihypertensive and hypnotic effect of tetrandrine on spontaneously hypertensive rats (SHR) and the possible mechanisms.
  
  
  METHODS
  Electroencephalography (EEG) and electromyography (EMG) were recorded in freely moving rats and the sleep parameters were analyzed with SleepSign software. The levels of serotonin (5-HT), norepinephrine (NE), dopamine (DA) and their metabolites were examined to investigate the underlying mechanisms by using HPLC-ECD. Blood pressure was measured by noninvasive blood pressure tail cuff test.
  
  
  RESULTS
  Tetrandrine (100mg/kg, i.g.) significantly suppressed blood pressure of SHR rats day by day during three days treatment. Meanwhile, tetrandrine remarkably improved the sleep efficiency by increasing total sleep time, rapid eye movement (REM) sleep and non-REM (NREM) sleep (including deep sleep and light sleep) time from the first day. Three days treatment of tetrandrine induced 5-HT concentration decrease in DRN, 5-HIAA concentration increase in LC and 5-HIAA/5-HT ratio increase in VTA and LC. In contrast, no changes in NE and DA concentrations in the DRN, VTA and LC occurred in SHR after tetrandrine treatment. These results indicate that modulation of 5-HT, its metabolite 5-HIAA and the 5-HIAA/5-HT ratio in DRN, VTA and LC are likely the mechanism of antihypertensive and hypnotic effects of tetrandrine at least in part.
  
  
  CONCLUSIONS
  This is the first observation that tetrandrine possesses both anti-hypertension and hypnotic effects in SHR and suggested that tetrandrine may be useful for the treatment of hypertension patients who accompanied with short sleep time and poor sleep efficiency.
authors.affiliation: Department Of Pharmacology, Peking University, School of Basic Medical Science, 38 Xueyuan Lu, Beijing 100191, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department Of Pharmacology, Peking University, School of Basic Medical Science, 38 Xueyuan Lu, Beijing 100191, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Yu
authors.affiliation: Department Of Pharmacology, Peking University, School of Basic Medical Science, 38 Xueyuan Lu, Beijing 100191, China.
authors.forename: Xue-Qiong
authors.initials: XQ
authors.lastname: Zhang
authors.affiliation: Department Of Pharmacology, Peking University, School of Basic Medical Science, 38 Xueyuan Lu, Beijing 100191, China.
authors.forename: Zhao-Fu
authors.initials: ZF
authors.lastname: Sheng
authors.affiliation: Department Of Pharmacology, Peking University, School of Basic Medical Science, 38 Xueyuan Lu, Beijing 100191, China.
authors.forename: Sheng-Jie
authors.initials: SJ
authors.lastname: Li
authors.affiliation: Department Of Pharmacology, Peking University, School of Basic Medical Science, 38 Xueyuan Lu, Beijing 100191, China.
authors.forename: Zi-Jun
authors.initials: ZJ
authors.lastname: Wang
authors.affiliation: Department Of Pharmacology, Peking University, School of Basic Medical Science, 38 Xueyuan Lu, Beijing 100191, China.
authors.forename: Xiang-Yu
authors.initials: XY
authors.lastname: Cui
authors.affiliation: Department Of Pharmacology, Peking University, School of Basic Medical Science, 38 Xueyuan Lu, Beijing 100191, China.
authors.forename: Su-Ying
authors.initials: SY
authors.lastname: Cui
authors.affiliation: Department Of Pharmacology, Peking University, School of Basic Medical Science, 38 Xueyuan Lu, Beijing 100191, China. Electronic address: zhyh@hsc.pku.edu.cn.
authors.forename: Yong-He
authors.initials: YH
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000737:chemistry / Q000494:pharmacology*; D044182:Benzylisoquinolines / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012890:Sleep / Q000187:drug effects*
chemical_list: D000959:Antihypertensive Agents; D044182:Benzylisoquinolines; C009438:tetrandrine
keywords: 5-HT; Hypertension; Sleep quality; Tetrandrine