Hyporeactivity of mesenteric vascular bed in endotoxin-treated rats.
Vascular reactivity and activation of the nitric oxide (NO) pathway were investigated in perfused mesenteric vascular bed removed from rats 5 h after i.p. injection of bacterial lipopolysaccharide (E. coli lipopolysaccharide, 30 mg kg -1). Lipopolysaccharide treatment induced hyporesponsiveness to noradrenaline. Maximal noradrenaline-induced vasoconstriction was significantly reduced in lipopolysaccharide-treated vs. untreated preparations. Continuous infusion of L-arginine (L-Arg) (0.2 mM) enhanced noradrenaline hyporeactivity of lipopolysaccharide-treated rats. N omega-Nitro-L-arginine methyl ester (L-NAME) (0.2 mM), a non-selective inhibitor of NO synthase, failed to completely restore the noradrenaline hyporeactivity of lipopolysaccharide-treated + L-Arg-infused mesenteric vascular bed. After L-NAME treatment. Methylene blue (10 microM), a guanylate cyclase inhibitor, produced no additional increase of noradrenaline vasoconstriction in lipopolysaccharide-treated + L-Arg-infused mesenteric vascular bed, suggesting that an NO-independent activation of guanylate cyclase may be excluded. In lipopolysaccharide-treated preparations, L-Arg (0.2 mM) elicited a significant increase in nitrite production, which was antagonized by L-NAME. In conclusion, lipopolysaccharide-induced noradrenaline hyporesponsiveness of rat resistance vessels can only be partially explained by NO overproduction. Other mechanisms, probably related to vasoconstriction, may be involved.
Mitolo-Chieppa
D
D
Institute of Pharmacology, Medical School, University of Bari, Italy.
Serio
M
M
Potenza
M A
MA
Montagnani
M
M
Mansi
G
G
Pece
S
S
Jirillo
E
E
Stoclet
J C
JC
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D008643:Mesentery / Q000098:blood supply / Q000187:drug effects*; D008751:Methylene Blue / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009573:Nitrites / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014655:Vascular Resistance / Q000187:drug effects*
D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D009573:Nitrites; D001120:Arginine; D019001:Nitric Oxide Synthase; D008751:Methylene Blue; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine