Recent studies have provided evidence that administration of E. coli lipopolysaccharides (LPS) to rats produces vascular hyporeactivity to catecholamines and other vasoconstrictor agents. The present study was carried out ex vivo on mesenteric vascular bed from LPS-injected rats in order to investigate the causes of vascular hyporesponsiveness as well as the role of L-arg/NO pathway in resistance blood vessels, during septic shock syndrome. The involvement of L-arg/NO pathway was evaluated by administration of L-arg, which produced a decrease of perfusion pressure in LPS-treated rats, whereas it was ineffective in control rats. Under these experimental conditions, L-NAME or L-NNA, inhibitors of NO production were unable to prevent L-arg vasorelaxation. Furthermore, dexamethasone pretreatment in endotoxaemic rats significantly reduced the vasorelaxation by L-arg, whereas it was ineffective to reverse vascular hyporeactivity occurring in septic shock; moreover, dexametasone significantly increased initial contraction peak induced by NA. In order to evaluate whether vascular hyporeactivity could be due to defects in calcium-dependent mechanisms, we tested the effect of ET-1, a vasoconstrictor peptide released by endothelium. In LPS-treated rats, ET-1 was able to enhance the contractile response to NA much more than in control rats. Our findings suggest that hyporesponsiveness in septic shock syndrome may depend on both activation of the L-arg/NO pathway and alterations in post-receptor mechanisms involving calcium handling.
|Translated title of the contribution||The role of pathway L-arginine/nitric oxide on vascular hyporeactivity in septic shock. Pharmacological study of endotoxin-injected rats|
|Number of pages||11|
|Journal||Rivista Italiana di Biologia e Medicina|
|Publication status||Published - 1995|
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