Endotoxin‐induced vasodilatation in anaesthetized rat skin involves nitric oxide and prostaglandin synthesis

Abstract

The effect of intradermally injected endotoxin on skin blood flow was investigated in anaesthetized male Wistar rats in vivo. Local skin blood flow changes were measured hourly for 6 h in the shaved dorsal skin with a laser‐Doppler flow probe and compared to changes in control sites which had been injected with 100 μl of phosphate‐buffered saline. By 3 h, skin blood flow increased above basal by 129 ± 27% and 186 ± 29% with 1 and 10 μg of endotoxin respectively. Blood flow remained significantly elevated at 6 h, the corresponding figures being 129 ± 24% and 154 ± 31% (P < 0.05, n = 6 rats, mean ± s.e.mean). In further experiments, the response to 3 μg of endotoxin was measured at 4 h and treatment with a cyclo‐oxygenase inhibitor, nitric oxide synthase inhibitors or a topical steroid all significantly inhibited this response (P < 0.05 in each case, n = 6 rats in each group with duplicate sites in each animal). Indomethacin 3 × 10−9 mol per site injected 3.5 h after injection of endotoxin suppressed the mean 4 h response to endotoxin by 78%; NG‐nitro‐l‐arginine methyl ester (l‐NAME) 10−7 mol per site suppressed the response by 95%; NG‐monomethyl‐l‐arginine (l‐NMMA) 10−7 mol per site suppressed the response by 50%; whereas the d‐isomer of NG‐monomethyl‐arginine 10−7 mol per site had no significant effect. Topical application of the corticosteroid, betamethasone 17‐valerate (1% solution) 18 h before injection of endotoxin inhibited the mean 4 h response to endotoxin by 66% and the 6 h response by 48%. In the same model, the vasodilator response to arachidonic acid was inhibited by both indomethacin and nitric oxide synthase inhibitors (P < 0.05 in each case). These data suggest that the microcirculatory vasodilator response to endotoxin and arachidonic acid injected locally involves both nitric oxide synthase and cyclo‐oxygenase in this in vivo model. 1992 British Pharmacological Society