Effects of lipopolysaccharide on the neuronal control of mesenteric vascular tone in rats: mechanisms involved.

Abstract

The aim of the present study was to investigate the effects of lipopolysaccharide (LPS) on the contractile response induced by electrical field stimulation (EFS) in rat mesenteric segments, as well as the mechanisms involved. Effects of LPS incubation for 2 or 5 h were studied in mesenteric segments from male Wistar rats. Vasomotor responses to EFS, nitric oxide (NO) donor DEA-NO, and noradrenaline (NA) were studied. Phosphorylated neuronal NO synthase protein expression was analyzed, and NO, superoxide anion (O2·), and peroxynitrite releases were also determined. Lipopolysaccharide increased EFS-induced vasoconstriction at 2 h. This increase was lower after 5-h preincubation. N-nitro-L-arginine methyl ester increased vasoconstrictor response only in control segments. Vasodilator response to DEA-NO was increased by LPS after 5-h preincubation and was decreased by O2· scavenger tempol. Basal NO release was increased by LPS. Electrical field stimulation-induced NO release was reduced by LPS compared with control conditions. Lipopolysaccharide exposure increased both O2· and peroxynitrite release. Vasoconstriction to exogenous NA was markedly increased by LPS compared with control conditions after 2-h incubation and remained unchanged after 5-h incubation. Short-term exposure of rat mesenteric arteries to LPS produced a time-dependent enhanced contractile response to EFS. The early phase (2 h) was associated to a reduction in NO from neuronal NO synthase and an enhanced response to NA. After 5 h of LPS exposure, this enhancement was reduced, because of restoration of the adrenergic component and maintenance of the nitrergic reduction.