title: Lipoteichoic acid from Staphylococcus aureus depresses contractile function of human arteries in vitro due to the induction of nitric oxide synthase.
abstract: The aim of this study was to clarify the role of Gram-positive organisms in the genesis of sepsis. In the present study, we investigated the effect of lipoteichoic acid (LTA) from the cell wall of Staphylococcus aureus on contractions elicited by norepinephrine (NE) in rings cut from human gastroepiploic arteries. LTA diminished the contractile response to NE. This attenuation began after several hours of exposure, whether or not endothelium was present. The cyclic guanosine monophosphate content of LTA-treated rings was higher than that of control rings, whether there was a functional endothelium. These LTA-mediated responses were reduced significantly by inhibitors of nitric oxide (NO) synthase and guanylate cyclase. All of this indicates that the main underlying cause of the vascular hyporeactivity to NE was a massive generation of No. In addition, cycloheximide, an inhibitor of inducible NO synthase, prevented the attenuation of NE-induced contractions caused by LTA. Thus, our results offer strong supporting evidence that the important factor in the genesis by Gram-positive organisms of a diminished contractile response to pressor drugs is their induction of inducible NO synthase in smooth muscle.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Kagoshima University School of Medicine, Japan.
authors.forename: I
authors.initials: I
authors.lastname: Tsuneyoshi
authors.forename: Y
authors.initials: Y
authors.lastname: Kanmura
authors.forename: N
authors.initials: N
authors.lastname: Yoshimura
mesh_terms: D000009:Abdominal Muscles / Q000098:blood supply*; D000368:Aged; D001158:Arteries / Q000187:drug effects; D006152:Cyclic GMP / Q000032:analysis; D003513:Cycloheximide / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000187:drug effects*; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009852:Omentum / Q000098:blood supply*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D013211:Staphylococcus aureus; D013682:Teichoic Acids / Q000494:pharmacology*; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D011500:Protein Synthesis Inhibitors; D013682:Teichoic Acids; D014662:Vasoconstrictor Agents; D009569:Nitric Oxide; C009900:lipoteichoic acid; D003513:Cycloheximide; D019001:Nitric Oxide Synthase; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D009638:Norepinephrine