Figure 2

Penicillin increases microvascular permeability in a BK-dependent manner. (A) Representative image of Evans blue extravasation of rat dorsal inboard skin induced by penicillin (n = 3). Rats were anesthetized and intracutaneously injected with 100 μL of penicillin at different dosages and then immediately intravenously injected with 5 mg/mL of Evans blue (1 mL). Ten minutes later, the rats were euthanized and the resultant blue spots in the dorsal inboard skin were scored. A diameter > 5 mm was considered positive. (B) Icatibant blocked penicillin-induced local vasopermeability (n = 8). Fifteen minutes after induction of anesthesia (50 mg/kg of pentobarbital), mice were intraplantarly injected with 10 μL of icatibant (0.5 mM) or normal saline (NS). Twenty minutes later, the mice were injected (i.v.) with 50 μL of 12.5 mg/mL Evans blue. Five minutes later, 10 μL of penicillin (400 KU/mL) or NS was administered by intraplantar injection in the paw. Thirty minutes later, the mice were euthanized. The paw tissues were collected and weighed. Evans blue was extracted by a 24 h incubation in formamide at 60 °C. The OD values were read at 620 nm. The concentration of the dye in the paw tissues was calculated from the standard curve of the Evans blue dye, and the dye content was expressed in microgram per gram of tissue. **P < 0.01.