Effect of GABA_A receptor antagonist bicuculline methiodide on hypotension in endotoxin-intoxicated rats

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 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.