Attenuation of endothelium-dependent hyperpolarizing factor by bacterial lipopolysaccharides

Endothelium-dependent hyperpolarizing factor (EDHF) is an important contributor to agonist-induced vascular dilation. Recent studies suggest that bacterial lipopolysaccharides attenuate endothelium-dependent dilation. Whether or not this effect is mediated through inhibition of EDHF is not known. We studied the in vitro influence of Escherichia coli lipopolysaccharides on endothelium-dependent smooth muscle dilation and hyperpolarization in porcine coronary arteries. Endothelium-intact porcine coronary arterial rings were examined after 20 h of incubation with either saline or E. coli lipopolysaccharides (100 mu g/ml). Endothelium-dependent dilation elicited by increasing concentrations of bradykinin was significantly attenuated by lipopolysaccharides. Baseline values of smooth muscle membrane potential were not influenced by lipopolysaccharides. However, lipopolysaccharides significantly attenuated bradykinin-induced smooth muscle membrane hyperpolarization. Our results suggest that attenuation of EDHF is an important mechanism through which lipopolysaccharides influence vascular dilation in severe sepsis.