LIPOTEICHOIC ACID FROM STAPHYLOCOCCUS-AUREUS DEPRESSES CONTRACTILE FUNCTION OF HUMAN ARTERIES IN-VITRO DUE TO THE INDUCTION OF NITRIC-OXIDESYNTHASE

The aim of this study was to clarify the role of Gram-positive organis ms in the genesis of sepsis. In the present study, we investigated the effect of lipoteichoic acid (LTA) from the cell wall of Staphylococcu s aureus on contractions elicited by norepinephrine (NE) in rings cut from human gastroepiploic arteries. LTA diminished the contractile res ponse to NE. This attenuation began after several hours exposure to LT A, and reached its maximum after 10 h of exposure, whether or not endo thelium was present. The cyclic guanosine monophosphate content of LTA -treated rings was higher than that of control rings, whether there wa s a functional endothelium. These LTA-mediated responses were reduced significantly by inhibitors of nitric oxide (NO) synthase and guanylat e cyclase. All of this indicates that the main underlying cause of the vascular hyporeactivity to NE was a massive generation of NO. In addi tion, cycloheximide, an inhibitor of inducible NO synthase, prevented the attenuation of NE-induced contractions caused by LTA. Thus, our re sults offer strong supporting evidence that the important factor in th e genesis by Gram-positive organisms of a diminished contractile respo nse to presser drugs is their induction of inducible NO synthase in sm ooth muscle.