The effect of the NO-synthase inhibitors on the contraction of the isolated bovine abdominal aorta induced by noradrenaline in the presence of LPS-endotoxins

Lipopolysaccharides (LPS) are endotoxins present in gramnegative bacteria, that cause of insufficiency in the cardiovascular system and damage to the internal organs. It has been shown that LPS and cytokines (TNF; IL-1 and IN F-gamma) act upon the endothelium of blood vessels, activiting the enzymes, inducible NO-synthase and cyclo-oxygenase (COX-2). At the same time, LPS i nduces marked synthesis and release of nitric oxide (NO) and prostacyclin ( PGI(2)). These endothelial mediators (NO and PGI(2)) relax the vascular smo oth muscle, thus bringing about proncunced vasodilatation and hypotension. They also cause a hyporeactive effect of the blood vessels to the vasoconst rictive drug. Having in mind theimportance of NO in the pathogenesis of sep tic shock, we undertook to examine the effect of the NO-synthase inhibitors , N-G-nitro-L-arginine methyl ester (L-NAME) and dexamethasone on the contr action of isolated bovine abdominal aorta induced by noradrenaline in the p resence of LPS. After an incubation of 4 hours, the lipopolysaccharide from E. coli O55:B5, depressed the contractile effect of noradrenaline on isolated bovine abdom inal aorta. This LPS depressing effect was antagonised by the NO-synthase i nhibitor (L-NAME). This L-NAME specific effect was confirmed by the adminis tration of L-arginine (as a NO donor), that antogonised the L-NAME effect, ie. it reversed the depressed contractile effect of noradrenaline in the pr esence of LPS. Dexamethasone, after an incubation period of 20 minutes, did not affect the decreased contractile effect of noradrenaline induced by LP S. However, after incubation for 60 minutes, this glucocorticosteroid elimi nated the LPS depressing effect on the isolated aorta contractions, produce d by noradrenaline. The obtained results show that the L-arginine NO system has an important role in the development of lowered reactivity of the isol ated bovine abdominal aorta to noradrenaline in the presence of LPS. Theref ore, an early application of the specific inhibitors NO-synthase and dexame thasone could prove very useful in the prevention of progressive vasodialat ation during septic shock.