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

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Abstract
1 The effect of intradermally injected endotoxin on skin blood flow was investigated in anaesthetized male Wistar rats in vivo. 2 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). 3 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). 4 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. 5 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%. 6 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). 7 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.

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