Allergy Asthma Immunol Res.  2018 Jan;10(1):52-61. 10.4168/aair.2018.10.1.52.

β₂-Adrenoceptor Blockade Deteriorates Systemic Anaphylaxis by Enhancing Hyperpermeability in Anesthetized Mice

• Yang W
• Shibamoto
• Kuda Y
• Zhang T
• Tanida M
• Kurata Y

• KMID: 2428850
• DOI: http://doi.org/10.4168/aair.2018.10.1.52

Abstract

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.

Keyword

Anaphylactic shock; Evans blue dye; epinephrine; β-blocker; vascular leakage; anesthetized mice

MeSH Terms

Adrenal Glands
Adrenalectomy
Anaphylaxis*
Animals
Arterial Pressure
Atenolol
Capillary Permeability
Epinephrine
Evans Blue
Hematocrit
Humans
Intestines
Kidney
Liver
Lung
Mesentery
Mice*
Mice, Inbred C57BL
Plasma
Propranolol
Spleen
Survival Rate
Terbutaline
Atenolol
Epinephrine
Evans Blue
Propranolol
Terbutaline

Figure

• 

  Fig. 1 The time schedule of the experiment. β-AR antagonists, agonist or saline, injection of each β-adrenoceptor antagonist, the β-adrenoceptor agonist terbutaline or saline (100 µL); Antigen, injection of ovalbumin antigen (3 µg in 100 µL saline); EB, injection of Evans blue dye; Hct, sampling of blood for the measurement of hematocrit; EB washout, the start of saline infusion into the right and left ventricles to washout Evans blue dye for 5 minutes.

• 

  Fig. 2 Effects of β-adrenoceptor antagonists or adrenalectomy on time-course changes in the mean blood pressure (A), survival rate (B), and hematocrit (Hct) (C). In (A), circle, the non-sensitized control group (n=7); inverted triangle, the sensitized control group (n=7); square, the ICI 118,551 group (n=7); diamond, the atenolol group (n=7); triangle, the propranolol group (n=7); star, the adrenalectomy group (n=7). Values are means±SEM; open symbols, P<0.05 vs baseline; #P<0.05 vs the sensitized control group. In (B), the symbols are the same as those of (A). In (C), orange bars, the values at baseline; blue bars, the values at 20 minutes after antigen injection. *P<0.05 vs baseline; #P<0.05 vs the sensitized control group.

• 

  Fig. 3 Effects of β-adrenoceptor antagonists or adrenalectomy on Evans blue dye content of organs. Values are means±SEM; #P<0.05 vs the sensitized control group.

• 

  Fig. 4 Effects of the β-adrenoceptor agonist terbutaline on time-course changes in the mean blood pressure (A) and hematocrit (Hct) (B). In (A), circle, the non-sensitized control group (n=7); inverted triangle, the sensitized control group (n=7); square, the terbutaline group (n=7). Values are means±SEM; open symbols, P<0.05 vs baseline; #P<0.05 vs the sensitized control group. In (B), orange bars, the values at baseline; blue bars, the values at 20 minutes after antigen injection. *P<0.05 vs baseline; #P<0.05 vs the sensitized control group.

• 

  Fig. 5 Effects of the β-adrenoceptor agonist terbutaline on Evans blue dye content of organs. Values are means±SEM; #P<0.05 vs the sensitized control group.

• 

  Fig. 6 Plasma concentrations of epinephrine (A) and norepinephrine (B) at 6 minutes after antigen injection. Values are means±SEM; #P<0.05 vs the non-sensitized control group.

• 

  Fig. 7 The summary of the content of the present study.

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