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KMID : 1225720180100010052
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Allergy, Asthma & Immunology Research : AAIR
2018 Volume.10 No. 1 p.52 ~ p.61
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β2-Adrenoceptor Blockade Deteriorates Systemic Anaphylaxis by Enhancing Hyperpermeability in Anesthetized Mice
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Yang Wei
Shibamoto Toshishige
Kuda Yuhichi
Zhang Tao
Tanida Mamoru
Kurata Yasutaka
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Abstract
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Purpose: Patients treated with propranolol, a nonselective β-adrenoceptor antagonist, develop severe anaphylaxis, but the mechanism remains unknown. We determined effects of β1- and β2-adrenoceptor antagonists on the anaphylaxis-induced increase in vascular permeability in mice.
Methods: In anesthetized ovalbumin-sensitized C57BL mice, mean arterial blood pressure (MBP) was measured, and Evans blue dye extravasation and hematocrit (Hct) were assessed at 20 minutes after antigen injection. The following pretreatment groups (n=7/group) were studied: (1) sensitized control (non-pretreatment), (2) propranolol, (3) the selective β2-adrenoceptor antagonist ICI 118,551, (4) the selective β1-adrenoceptor antagonist atenolol, (5) adrenalectomy, (6) the selective β2-adrenoceptor agonist terbutaline, and (7) non-sensitized groups.
Results: The antigen injection decreased MBP, and increased Hct and vascular permeability in the kidney, lung, mesentery, and intestine, but not in the liver or spleen. Pretreatment with ICI 118,551, propranolol and adrenalectomy, but not atenolol, reduced the survival rate and augmented the increases in Hct and vascular permeability in the kidney, intestine, and lung as compared with the sensitized control group. Pretreatment with terbutaline abolished the antigen-induced alterations. Plasma epinephrine levels were increased significantly in the sensitize control mice.
Conclusions: Blockade of β2-adrenoceptor can deteriorate systemic anaphylaxis by augmenting hyperpermeability-induced increase in plasma extravasation by inhibiting beneficial effects of epinephrine released from the adrenal glands in anesthetized mice.
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KEYWORD
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Anaphylactic shock, Evans blue dye, epinephrine, β-blocker, vascular leakage, anesthetized mice
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