title: Pretreatment with Evans blue, a stimulator of BK(Ca) channels, inhibits compound 48/80-induced shock, systemic inflammation, and mast cell degranulation in the rat.
abstract: The present study demonstrated that intravenous injection of a high dose of compound 48/80 to the rat induced 50% drop, within a few min, in the mean arterial pressure and pulse pressure as well as systemic inflammatory plasma leakage that might lead to circulatory and respiratory failure. We also investigated whether pretreatment with Evans blue, a stimulator of BK(Ca) channels, could exert inhibitory effect against compound C48/80-induced allergic circulatory shock and systemic inflammation. Different groups of Sprague-Dawley rats received an intravenous injection of a dose of Evans blue (0, 5, 10, or 50 mg/kg) just 20 s prior to injection of compound 48/80 (200 μg/kg, over 2 min). The present study found that pretreatment with Evans blue in a dose of 10 or 50 mg/kg exerted acute inhibitory effect on compound 48/80-induced sudden drop in mean arterial and pulse pressures. We also showed that pretreatment with Evans blue in a dose of 5, 10, or 50 mg/kg significantly inhibited compound 48/80-induced extensive plasma extravasation, mast cell degranulation, and edema formation in various organs including the airways, esophagus, and skin. Pretreatment with Evans blue 50 mg/kg 1 h earlier exhibited longer-term inhibitory effect on compound 48/80-induced arterial hypotension and systemic inflammation. We concluded that Evans blue pretreatment prevented rats from compound 48/80-triggered allergic shock and systemic inflammation, possibly mainly through inhibition of mast cell degranulation. Evans blue might be potentially useful in elucidating the mechanism and acting as a therapeutic agent of allergic shock and systemic inflammation.
authors.affiliation: Department of Biomedical Science and Environmental Biology, College of Life Sciences, Kaohsiung Medical University, Kaohsiung City, Taiwan.
authors.forename: Yaw-Syan
authors.initials: YS
authors.lastname: Fu
authors.forename: Su-Yu
authors.initials: SY
authors.lastname: Kuo
authors.forename: Hsuan-Yea
authors.initials: HY
authors.lastname: Lin
authors.forename: Chun-Lin
authors.initials: CL
authors.lastname: Chen
authors.forename: Shi-Ying
authors.initials: SY
authors.lastname: Huang
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Wen
authors.forename: Kun-Zer
authors.initials: KZ
authors.lastname: Lee
authors.forename: Hung-Tu
authors.initials: HT
authors.lastname: Huang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D015550:Cell Degranulation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D005070:Evans Blue / Q000494:pharmacology*; D007249:Inflammation / Q000139:chemically induced / Q000517:prevention & control*; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000819:agonists*; D008297:Male; D008407:Mast Cells / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D056152:Respiratory Rate / Q000187:drug effects; D012769:Shock / Q000139:chemically induced / Q000517:prevention & control*; D014699:Venules / Q000187:drug effects / Q000473:pathology; D003189:p-Methoxy-N-methylphenethylamine / Q000037:antagonists & inhibitors* / Q000633:toxicity
chemical_list: D000893:Anti-Inflammatory Agents; D051036:Large-Conductance Calcium-Activated Potassium Channels; D003189:p-Methoxy-N-methylphenethylamine; D005070:Evans Blue