Time- and surgery-dependent effects of lipopolysaccharide on gut, cardiovascular and nitric oxide functions

Lipopolysaccharide (LPS) is considered a major effector of hypotension in s eptic shock, partly through increasing nitric oxide (NO) formation. LPS-act ivation of leukocytes that express cytokines which induce NO synthase (iNOS ) has also been considered an important contributor to shock. However, LPS, cytokines, and NO are not necessarily associated with hypotensive shock. W e investigated whether the timing of LPS injection after initial surgery co uld influence responses to LPS. E. coli LPS (17 mg/kg 0111:B4 and 026:B6 se rotypes) was injected 15 or 120 min after tracheal and femoral cannulation in the anesthetized rat. LPS caused hypotension for 2 h when injected 15 mi n (early injection) after initial surgery. LPS decreased blood pressure for only 15 min when injected 2 h (late injection) after initial surgery, Plas ma NO was increased and leukocytes were decreased after both the early and late LPS injection. Blood pressure responded the same when a second surgery (ileal cannulation and luminal perfusion) followed the early or preceded t he late LPS injection. Ileal NO secretion increased and effective mucosal b lood flow decreased when LPS followed gut surgery, but these did not change when gut surgery followed LPS. Plasma NO was increased and leukocytes were decreased when LPS followed gut surgery, but these did not change when gut surgery followed LPS. Ileal water absorption was not affected by LPS. Thes e observations suggest that a desensitization to the hypotensive effect of LPS develops with time after an initial trauma. An additional gut trauma do es not change the blood pressure response, but does have effects on leukocy te sequestration and NO synthesis. NO synthesis alone could not explain the effects on blood pressure.