Bacterial lipopolysaccharide-induced hyporeactivity in perfused rat resistance vessels: Modulating effects of dexamethasone

The present study was carried out on mesenteric vascular bed from LPS-injected rats in order to investigate possible mechanisms underlying hyporesponsiveness in resistance blood vessels in the course of septic shock syndrome. The involvement of L-arginine (L-Arg)/nitric oxide (NO) pathway was evaluated by administration of L-Arg, which produced a decrease in perfusion pressure in LPS-treated rats, whereas it was ineffective in control rats. Of note, dexamethasone (DEX) pretreatment in endotoxaemic rats significantly reduced the vasorelaxation by L-Arg; however, this non selective inhibitor of inducible-NOS expression was not able to prevent noradrenaline (NA) hyporeactivity. Furthermore, in order to evaluate whether hyporesponsiveness could be due to an altered contraction mechanism, the effect of endothelin (ET)-1 was tested. This peptide was able to markedly enhance the contractile response to noradrenaline in LPS-treated rats. Collectively, our findings suggest that vascular hyporesponsiveness during septic shock can only be partially explained by activation of the L-Arg/NO pathway. Other mechanisms, probably related to smooth muscle cell contractility, may be involved.