PMID- 9536520
OWN - NLM
STAT- MEDLINE
DCOM- 19980601
LR  - 20211109
IS  - 0255-6596 (Print)
IS  - 0255-6596 (Linking)
VI  - 22
IP  - 1
DP  - 1998 Jan
TI  - Beneficial effects of tetramethylpyrazine, an active constituent of Chinese 
      herbs, on rats with endotoxemia.
PG  - 46-54
AB  - Tetramethylpyrazine, an inhibitor of phosphodiesterase, has been widely used for 
      treatment of cardiovascular diseases in China. Here, we investigate the effects 
      of tetramethylpyrazine on hypotension, vascular hyporeactivity to norepinephrine 
      (NE), release of tumor necrosis factor-alpha (TNF alpha) and nitric oxide (NO) in 
      a rat model of circulatory shock induced by bacterial endotoxin (E. coli 
      lipopolysaccharide, LPS). Male Wistar-Kyoto rats were anesthetized and 
      instrumented for the measurement of mean arterial pressure (MAP) and heart rate 
      (HR). Injection of LPS (10 mg/kg, i.v.) resulted in a fall in MAP and an increase 
      of HR. In contrast, animals pretreated with tetramethylpyrazine (10 
      micrograms/kg, i.p. at 30 min prior to LPS) maintained a significantly higher 
      MAP, but tachycardia was further enhanced at 60 min and 120 min when compared to 
      rats given only LPS (LPS-rats). The pressor effect of NE (1 microgram/kg, i.v.) 
      was also significantly reduced after treatment of rats with LPS. Similarly, the 
      thoracic aorta obtained from rats after in vivo studies showed a significant 
      reduction in the contractile responses elicited by NE (1 microM). Pretreatment of 
      LPS-rats with tetramethylpyrazine partially, but significantly, prevented this 
      LPS-induced hyporeactivity to NE in vivo and ex vivo. The injection of LPS 
      resulted in a significant increase in the plasma TNF alpha level at 60 min, 
      whereas the effect of LPS on the plasma nitrate (an indicator of NO formation) 
      level increased in a time-dependent manner. This increment of both TNF alpha and 
      nitrate levels induced by LPS was significantly reduced in LPS-rats pretreated 
      with tetramethylpyrazine. The early hypotension caused by LPS was slightly, but 
      significantly, prevented by pretreatment with tetramethylpyrazine, suggesting 
      that tetramethylpyrazine affects the endothelial constitutive NOS (eNOS). This 
      was examined by the effect of tetramethylpyrazine on acetylcholine (ACh, 1 
      microM)-induced relaxation in rats treated with tetramethylpyrazine for 4 h. 
      However, tetramethylpyrazine had no significant effects on the ACh-induced 
      relaxation, indicating that tetramethylpyrazine does not affect the activity of 
      eNOS. Thus, tetramethylpyrazine attenuates the early hypotension and the delayed 
      circulatory failure caused by endotoxin in the rat. These effects may be due to 
      inhibition of the release of circulation factors and TNF alpha, which usually 
      reveal synergism upon the induction of iNOS.
FAU - Liao, M H
AU  - Liao MH
AD  - Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan, 
      R.O.C.
FAU - Wu, C C
AU  - Wu CC
FAU - Yen, M H
AU  - Yen MH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - China (Republic : 1949- )
TA  - Proc Natl Sci Counc Repub China B
JT  - Proceedings of the National Science Council, Republic of China. Part B, Life 
      sciences
JID - 8502426
RN  - 0 (Nitrates)
RN  - 0 (Phosphodiesterase Inhibitors)
RN  - 0 (Pyrazines)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - V80F4IA5XG (tetramethylpyrazine)
RN  - X4W3ENH1CV (Norepinephrine)
SB  - IM
MH  - Animals
MH  - Blood Pressure/drug effects
MH  - Endotoxemia/*drug therapy/physiopathology/prevention & control
MH  - Heart Rate/drug effects
MH  - Hypotension/drug therapy/prevention & control
MH  - In Vitro Techniques
MH  - Male
MH  - *Medicine, Chinese Traditional
MH  - Nitrates/blood
MH  - Nitric Oxide/physiology
MH  - Norepinephrine/pharmacology
MH  - Phosphodiesterase Inhibitors/*therapeutic use
MH  - *Plants, Medicinal
MH  - Pyrazines/*therapeutic use
MH  - Rats
MH  - Rats, Inbred WKY
MH  - Tumor Necrosis Factor-alpha/physiology
MH  - Vasoconstriction/drug effects
EDAT- 1998/04/16 00:00
MHDA- 1998/04/16 00:01
CRDT- 1998/04/16 00:00
PHST- 1998/04/16 00:00 [pubmed]
PHST- 1998/04/16 00:01 [medline]
PHST- 1998/04/16 00:00 [entrez]
PST - ppublish
SO  - Proc Natl Sci Counc Repub China B. 1998 Jan;22(1):46-54.