Inhibition of nitric oxide synthase in experimental gram-negative sepsis

Evans, T. , Carpenter, A., Silva, A. and Cohen, J. (1994) Inhibition of nitric oxide synthase in experimental gram-negative sepsis. Journal of Infectious Diseases, 169(2), pp. 343-349. (PMID:7508968)

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Abstract

Nitric oxide (NO) has been proposed as a mediator of hypotension in septic shock. The aim of this study was to determine whether an inhibitor of NO production, NG-monomethyl-L-arginine (L-NMMA), was able to protect against death in two murine models of experimental gram-negative sepsis. L-NMMA (3-300 mg kg-1) did not improve survival in intravenous or intraperitoneal models of sepsis. Seven h after intravenous infection, L-NMMA (100 mg/kg-1) reduced serum nitrite plus nitrate levels (NO breakdown products) from 774 microM in control-treated animals to 282 microM in L-NMMA-treated animals (P < .001). This compared to a level of 103 microM in uninfected mice. L-NMMA produced little change in bacterial load following infection and did not increase hepatic damage, as measured by serum levels of ornithine carbamoyltransferase. Thus, while L-NMMA may reverse the hyporesponsiveness of peripheral circulation in sepsis, it was unable to prevent death in these models of gram-negative septic shock.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Evans, Professor Tom
Authors: Evans, T., Carpenter, A., Silva, A., and Cohen, J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Journal of Infectious Diseases
Publisher:Infectious Diseases Society of America
ISSN:0022-1899
ISSN (Online):1537-6613

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