Interactive contribution of NK 1 and kinin receptors to the acute inflammatory oedema observed in response to noxious heat stimulation: studies in NK 1 receptor knockout mice

Scald injury in Sv129+C57BL/6 mice induced a temperature and time dependent oedema formation as calculated by the extravascular accumulation of [ 125 I]‐albumin. Oedema formation was suppressed in NK 1 knockout mice compared to wildtypes at 10 ( P <0.01) and 30 min ( P <0.001). However, at 60 min a similar degree of extravasation was observed in the two groups. Kinin B 1 (des‐Arg 10 Hoe 140; 1 μmol kg −1 ) and B 2 (Hoe 140; 100 nmol kg −1 ) antagonists caused an inhibition of oedema in wildtype mice at 10 and 30 min ( P <0.001), but not at 60 min or at 30 min in NK 1 receptor knockout mice. The inhibition of thermic oedema by des‐Arg 10 Hoe 140 was reversed by des‐Arg 9 bradykinin (0.1 μmol kg −1 ; P <0.01) and also observed with a second B 1 receptor antagonist (des‐Arg 9 Leu 8 bradykinin; 3 μmol kg −1 ; P <0.01). Furthermore des‐Arg 10 Hoe 140 had no effect on capsaicin (200 μg ear −1 ) ear oedema, but this was significantly reduced with Hoe 140 ( P <0.05). Scalding induced a large neutrophil accumulation at 4 h, as assessed by myeloperoxidase assay ( P <0.001). This was not suppressed by NK 1 receptor deletion or kinin antagonists. These results confirm an essential role for the NK 1 receptor in mediating the early, but not the delayed phase of oedema formation or neutrophil accumulation in response to scalding. The results also demonstrate a pivotal link between the kinins and sensory nerves in the microvascular response to burn injury, and for the first time show a rapid involvement of the B 1 receptor in murine skin.British Journal of Pharmacology (2001) 134 , 1805–1813; doi: 10.1038/sj.bjp.0704436