TY - JOUR
T1 - Effect of GABAA receptor antagonist bicuculline methiodide on hypotension in endotoxin-intoxicated rats
AU - Hsu, Dur Zong
AU - Liu, Ming Yie
N1 - Funding Information:
This research was supported, in part, by grant DOH92-TD-1009 from the Taiwan Department of Health. We thank Dr. S.T. Wang for statistical analysis and comments. We also thank Bill Franke for revising our English.
PY - 2004/8/5
Y1 - 2004/8/5
N2 - γ-Aminobutyric acid (GABA) receptor plays an important regulatory role in human and animal blood pressure; however, whether a GABAergic mechanism is involved in endotoxin intoxication-associated hypotension has never been reported. In vivo effect of the GABAA receptor antagonist bicuculline methiodide (BMI) on mean arterial pressure (MAP), heart rate (HR), and serum nitrite levels were investigated in endotoxin (lipopolysaccharide; LPS)-treated rats. BMI increased MAP and decreased HR in LPS-stimulated rats. DOAV ([deamino-Pen, O-Me-Tyr, Arg3]-vasopressin), an arginine vasopressin (AVP) antagonist, reversed the hemodynamic improvement resulted from BMI in LPS-intoxicated rats. Based on a two-factor (BMI treatment by LPS dose) factorial design, BMI reduced the serum nitrite production induced by LPS. DOAV plus BMI, however, did not affect the serum nitrite level in LPS-intoxicated rats. Thus, GABA receptor antagonist BMI might attenuate hypotension in endotoxin intoxication in rats.
AB - γ-Aminobutyric acid (GABA) receptor plays an important regulatory role in human and animal blood pressure; however, whether a GABAergic mechanism is involved in endotoxin intoxication-associated hypotension has never been reported. In vivo effect of the GABAA receptor antagonist bicuculline methiodide (BMI) on mean arterial pressure (MAP), heart rate (HR), and serum nitrite levels were investigated in endotoxin (lipopolysaccharide; LPS)-treated rats. BMI increased MAP and decreased HR in LPS-stimulated rats. DOAV ([deamino-Pen, O-Me-Tyr, Arg3]-vasopressin), an arginine vasopressin (AVP) antagonist, reversed the hemodynamic improvement resulted from BMI in LPS-intoxicated rats. Based on a two-factor (BMI treatment by LPS dose) factorial design, BMI reduced the serum nitrite production induced by LPS. DOAV plus BMI, however, did not affect the serum nitrite level in LPS-intoxicated rats. Thus, GABA receptor antagonist BMI might attenuate hypotension in endotoxin intoxication in rats.
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U2 - 10.1016/j.tox.2004.04.001
DO - 10.1016/j.tox.2004.04.001
M3 - Article
C2 - 15212817
AN - SCOPUS:2942746224
SN - 0300-483X
VL - 200
SP - 213
EP - 219
JO - Toxicology
JF - Toxicology
IS - 2-3
ER -