SHORT-TERM EXPOSURE TO LIPOPOLYSACCHARIDE IS ASSOCIATED WITH MICROVASCULAR CONTRACTILE DYSFUNCTION IN-VIVO

The purpose of this study was to determine whether short-term exposure of resistance arterioles to lipopolysaccharide in situ is associated with changes in vasomotor tone. Using intravital microscopy, we found that suffusion of Escherichia coli lipopolysaccharide (3 mu g/ml) over hamster cheek pouch arterioles for 1 h was associated with a signific ant immediate biphasic response: vasoconstriction followed by vasodila tion (p<0.05). The former was attenuated by indomethacin, and the latt er by SK&F 108566, a selective, non-peptide angiotensin II receptor an tagonist (p<0.05). The nitric oxide synthase inhibitor, N-G-L-nitro ar ginine, had no significant effects on lipopolysaccharide-induced respo nses. Allopurinol, a scavenger of reactive oxygen species, significant ly attenuated lipopolysaccharide-induced vasodilation. Acetylcholine- and nitroglycerin-induced vasodilation were significantly potentiated after lipopolysaccharide. These responses were recorded in the absence of any significant changes in systemic arterial blood pressure. Colle ctively, these data suggest that short-term exposure of the peripheral microcirculation to lipopolysaccharide in situ is associated with an ischemia-reperfusion-like injury. These changes may contribute to end organ failure observed several hours after exposure to lipopolysacchar ide.