Effects of GW274150 a novel and selective inhibitor of iNOS activity in acute lung inflammation

摘要

class="enumerated" style="list-style-type:decimal">The aim of this study was to investigate the effect of , a novel, potent and selective inhibitor of inducible nitric oxide synthase (iNOS) activity in a model of lung injury induced by carrageenan administration in the rats.Injection of carrageenan into the pleural cavity of rats elicited an acute inflammatory response characterized by: fluid accumulation in the pleural cavity which contained a large number of polymorphonuclear cells (PMNs) as well as an infiltration of PMNs in lung tissues and subsequent lipid peroxidation, and increased production of nitrite/nitrate (NOx), tumour necrosis factor α (TNF-α) and interleukin-1β (IL-1β).All parameters of inflammation were attenuated in a dose-dependent manner by (2.5, 5 and 10 mg kg⁻¹ injected i.p. 5 min before carrageenan).Carrageenan induced an upregulation of the intracellular adhesion molecules-1 (ICAM-1), as well as nitrotyrosine and poly (ADP-ribose) (PAR) as determined by immunohistochemical analysis of lung tissues.The degree of staining for the ICAM-1, nitrotyrosine and PAR was reduced by . These results clearly confirm that NO from iNOS plays a role in the development of the inflammatory response by altering key components of the inflammatory cascade. may offer a novel therapeutic approach for the management of various inflammatory diseases where NO and related radicals have been postulated to play a role.