Induction of nitric oxide production by polyosides from the cell walls of Streptococcus mutans OMZ 175, a gram-positive bacterium, in the rat aorta.
The cardiovascular dysfunctions associated with septic shock induced by gram-negative or gram-positive bacteria (gram-positive or gram-negative septic shock) are comparable. In gram-negative septic shock, lipopolysaccharide (LPS) induces nitric oxide (NO) synthase, which contributes to the vascular hypotension and hyporeactivity to vasoconstrictors. The role of NO in gram-positive septic shock and the nature of the bacterial wall components responsible for the vascular effects of gram-positive bacteria are not well known. This study investigated the vascular effects of cell wall serotype polyosides, rhamnose glucose polymers (RGPs), from Streptococcus mutans, in comparison with lipoteichoic acid (LTA) from Staphylococcus aureus, on the induction of NO synthase activity in the rat aorta. We show that 10 microg of both RGPs and LTA per ml induced hyporeactivity to noradrenaline, L-arginine-induced relaxation, increases of 2.2- and 7.8-fold, respectively, of cyclic GMP production, and increases of 7- and 12-fold in nitrite release. All of these effects appeared after several hours of incubation and were inhibited by N(omega)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthase. Electron paramagnetic resonance spin trapping experiments demonstrated directly that RGPs and LTA induced NO overproduction (four- to eightfold, respectively) in rat aortic rings; this production was inhibited by L-NAME and prevented by dexamethasone. These results demonstrate directly the induction of NO production in vascular tissue by LTA and show that another, chemically different component of gram-positive bacteria can also have these properties. This result suggests that different components of the gram-positive bacterial wall could be implicated in the genesis of cardiovascular dysfunctions observed in gram-positive septic shock.
Martin
V
V
Laboratoire de Pharmacologie et de Physiopathologie Cellulaires, URA CNRS 600, Faculté de Pharmacie, Université Louis Pasteur de Strasbourg, France.
Kleschyov
A L
AL
Klein
J P
JP
Beretz
A
A
D000818:Animals; D001011:Aorta / Q000382:microbiology*; D002473:Cell Wall / Q000737:chemistry; D006152:Cyclic GMP / Q000032:analysis; D004578:Electron Spin Resonance Spectroscopy; D004730:Endothelium, Vascular / Q000502:physiology; D005947:Glucose / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D012210:Rhamnose / Q000494:pharmacology*; D013295:Streptococcus mutans / Q000737:chemistry*; D013682:Teichoic Acids / Q000494:pharmacology
D008070:Lipopolysaccharides; D013682:Teichoic Acids; D009569:Nitric Oxide; C009900:lipoteichoic acid; D006152:Cyclic GMP; D005947:Glucose; D012210:Rhamnose