Effects of adrenaline or endotoxin tolerance states on mesenteric blood flow in endotoxaemia

Endotoxic shock is associated with release of catecholamines as well as decreased mesenteric vascular perfusion, which is thought to cause remote organ injury. Adrenaline tolerance was reported to decrease mortality in endotoxic shock and have cross-tolerance with endotoxin tolerance. Our aim was to investigate the effect of these two tolerance conditions on the lipopolysaccharide (LPS)-induced decrease in mesenteric blood flow (MBF).

Adrenaline tolerance was developed by injecting 0.03 mg/kg adrenaline to Swiss-albino mice, gradually increasing the dose to 2 mg/kg over 5 days. Endotoxin tolerance was developed by injecting saline for 4 days and LPS 1 mg/kg at the fifth day. Control animals were injected with saline for 5 days. At 72 h after completion of injections, half of the animals in each group were challenged with saline and the other half with 20 mg/kg LPS, at 0 h. Mesenteric blood flow was measured at 4 and 24 h.

Neither endotoxin nor adrenaline tolerance prevented an LPS-induced decrease in MBF.

A low dose of LPS prior to a higher dose does not prevent an LPS-induced decrease in MBF and may actually prime for a decrease. Also, catecholamines are not primary mediators of LPS-induced decreases in MBF.