Angiopoietin-2 Is Released Only at Late Phase of Systemic Anaphylaxis in Awake Rats

Angiopoietin (Angpt)-2, a endothelium derived permeability-increasing endothelial growth factor, is released in response to anaphylactic mediators such as histamine and leukotrienes, and is involved in vascular leakage of sepsis and acute lung injury. We hypothesized that Angpt-2 is released and may augment hyperpermeability during anaphylactic hypotension. Thus, we determined the plasma Angpt-2 levels during anaphylactic hypotension in awake ovalbumin-sensitized Sprague Dawley rats. The sensitized (n = 6), and non-sensitized (n = 6) rats were intravenously injected with the antigen (0.6 mg) under un-anesthetized state. Mean blood pressure (MBP) was measured, and hematocrit (Hct) and plasma Angpt-2 levels were assessed at baseline and at 6, 20 and 60 min, and 2, 6 and 24 h after antigen. In sensitized rats, at 6 min after antigen, MBP decreased to the nadir of 58±10 (SD) mmHg from the baseline (106±3 mmHg). Hct increased to the peak of 55±3% from the baseline (42±1%) at 20 min after antigen, followed by a gradual decline. Consequently, MBP and Hct recovered to the baseline at 1 and 2 h, respectively. These results suggest that anaphylaxis-induced plasma extravasation peaked within 1 h. Plasma Angpt-2 levels did not increase significantly from the baseline of 20±2 ng/ml until 1 h after antigen (27±3 ng/ml), thereafter increased gradually reaching the peak of 54±6 ng/ml (2.7 fold baseline) at 6 h, followed by a return to the baseline at 24 h. Angpt-2 is released only at late phase and is not involved in early vascular leak during anaphylactic hypotension in awake rats.