Abstract
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(ω)-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 μM), 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.
| Original language | English |
|---|---|
| Pages (from-to) | 175-182 |
| Number of pages | 8 |
| Journal | European Journal of Pharmacology |
| Volume | 309 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Aug 8 1996 |
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Keywords
- L-Arginine
- Lipopolysaccharide
- Mesenteric vascular bed
- Nitric oxide (NO)
- Nitric oxide (NO) synthase
- Rat
- Septic shock
ASJC Scopus subject areas
- Cellular and Molecular Neuroscience
- Pharmacology
Cite this
Hyporeactivity of mesenteric vascular bed in endotoxin-treated rats. / Mitolo-Chieppa, Delia; Serio, Miralma; Potenza, M. Assunta; Montagnani, Monica; Mansi, Gianfranco; Pece, Salvatore; Jirillo, Emilio; Stoclet, Jean Claude.
In: European Journal of Pharmacology, Vol. 309, No. 2, 08.08.1996, p. 175-182.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Hyporeactivity of mesenteric vascular bed in endotoxin-treated rats
AU - Mitolo-Chieppa, Delia
AU - Serio, Miralma
AU - Potenza, M. Assunta
AU - Montagnani, Monica
AU - Mansi, Gianfranco
AU - Pece, Salvatore
AU - Jirillo, Emilio
AU - Stoclet, Jean Claude
PY - 1996/8/8
Y1 - 1996/8/8
N2 - 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(ω)-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 μM), 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.
AB - 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(ω)-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 μM), 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.
KW - L-Arginine
KW - Lipopolysaccharide
KW - Mesenteric vascular bed
KW - Nitric oxide (NO)
KW - Nitric oxide (NO) synthase
KW - Rat
KW - Septic shock
UR - http://www.scopus.com/inward/record.url?scp=0030575538&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0030575538&partnerID=8YFLogxK
U2 - 10.1016/0014-2999(96)00347-0
DO - 10.1016/0014-2999(96)00347-0
M3 - Article
C2 - 8874136
AN - SCOPUS:0030575538
VL - 309
SP - 175
EP - 182
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
SN - 0014-2999
IS - 2
ER -