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

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.

Vascular permeability and Evans blue dye: a physiological and pharmacological approach.

The acute inflammatory response consists of three main vascular effects: vasodilatation and increased blood flow, increased vascular permeability, and leukocytosis into the injured tissues. All three events are induced relatively quickly, and, for all three, the pattern of response is complex but consistent. Evans blue dye is an alkaline stain, so there is an affinity for the alkali in the acidic nucleus. The use of Evans blue dye as an in vivo marker through vascular permeability, facilitates the investigation of the effect of pathological changes in various disorders mainly, immunological disorders, inflammatory disorders, cardiovascular diseases like atherosclerosis, myocardial infarction, cancers and others. Endothelials have pathophysiological roles in pulmonary hypertension, arterial hypertension, atherosclerosis, cerebral vasospasm and inflammatory processes. The present review discussed with role of evans blue in the assessment of vascular permeability for the various pharmacological activities which are helps for the future investigations

Acute Changes in Regional Brain Edema Following Experimental Localized Brain Injury

This study was undertaken to identify acute changes and mechanism of traumatic brain edema in the rabit by measuring the regional specific gravities and water content with Evans blue dye staining. After delivery of brain injury on the frontal area, animals were sacrificed at 30 minutes, 2, 4 and 6 hours. Specific gravity data collection of regional brain tissue was taken in the serial copper sulfate gravity solution. The regions tested included frontal lobe, occipital lobe, basal ganglia, cerebellum, pons and medulla. Specific gravity data and Evans blue dye staining with spread were compared with those from similar areas in the uninjured anesthetized rabbits to test for brain edema. The results obtained were as follows: 1) Immediately following brain impact, almost all animals in this study demonstrated temporary respiratory arrest. The mean duration of respiratory arrest in experimental animals was 15+/-3 seconds. There was no correlation between length of respiratory arrest and either gross intracranial pathology or brain edema data. 2) The specific gravities in both hemispheres were same in control animals and were not affected by the duration of anesthesia. 3) Significant decrease of specific gravity was identified in the both supratentorial regions at 30 minutes, 2 and 4 hours after trauma. This finding was more prominent in the contused side. No significant changes occurred in the cerebellum but significant decrease of specific gravity occurred in medulla at 6 hours. 4) Almost brain water content was increased as the time course and arrived on peak value at 4 hours and decreased at 6 hours after trauma in the supratentorial regions. 5) Evans blue dye staining occurred in the contusion area at 30 minutes after trauma and spread to surrounding cortex and subcortex but dye density was decreased with time. These results suggest that traumatic brain edema may originate from vasogenic mechanism due to dysfunction of blood-brain barrier and this edema may spread to both cerebral hemispheres and brain stem.