Effect of GABA(A) receptor antagonist bicuculline methiodide on hypotension in endotoxin-intoxicated rats.
Gamma-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 GABA(A) 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.
Hsu
Dur-Zong
DZ
Department of Environmental and Occupational Health, National Cheng Kung University Medical College, 138 Sheng-Li Road, Tainan 704, Taiwan.
Liu
Ming-Yie
MY
D000818:Animals; D001127:Arginine Vasopressin / Q000031:analogs & derivatives* / Q000494:pharmacology; D001640:Bicuculline / Q000031:analogs & derivatives* / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004731:Endotoxins / Q000633:toxicity*; D018756:GABA Antagonists / Q000494:pharmacology*; D058787:GABA-A Receptor Antagonists; D006339:Heart Rate / Q000187:drug effects; D007022:Hypotension / Q000139:chemically induced* / Q000503:physiopathology / Q000517:prevention & control*; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D009573:Nitrites / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D004731:Endotoxins; D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D008070:Lipopolysaccharides; D009573:Nitrites; D014662:Vasoconstrictor Agents; D001127:Arginine Vasopressin; C017069:bicuculline methiodide; C028888:argipressin, deaminopenicillamine(1)-O-methyl-Tyr(2)-; D001640:Bicuculline