The interaction of adrenergic agonists and/or antagonists with the adrenergic receptors expressed on immunologically active cells including macrophages plays an important role in regulation of inflammatory responses. Our study investigated the effects of carvedilol, a unique vasodilating beta-adrenergic antagonist, and endogenous adrenergic agonists (adrenalin, noradrenalin, and dopamine) and/or antagonists (prazosin, atenolol) on lipopolysaccharide-stimulated nitric oxide (NO) production from murine macrophage cell line RAW 264.7. The production of NO was determined as the concentration of nitrites in cell supernatants (Griess reaction) and inducible nitric oxide synthase (iNOS) protein expression (Western blot analysis). Scavenging properties against NO were measured electrochemically. Carvedilol in a concentration range of 1, 5, 10 and 25 microM inhibited iNOS protein expression and decreased the nitrite concentration in cell supernatants. Adrenalin, noradrenalin or dopamine also inhibited the iNOS protein expression and the nitrite accumulation. Prazosine and atenolol prevented the effect of both carvedilol and adrenergic agonists on nitrite accumulation and iNOS expression in lipopolysaccharide-stimulated cells. These results, together with the absence of scavenging properties of carvedilol against NO, imply that both carvedilol and adrenergic agonists suppress the lipopolysaccharide-evoked NO production by macrophages through the activation and modulation of signaling pathways connected with adrenergic receptors.

• MeSH
• adrenergní receptory metabolismus   účinky léků   MeSH
• agonisté adrenergních receptorů farmakologie   MeSH
• alfa blokátory farmakologie   MeSH
• beta blokátory aplikace a dávkování   farmakologie   MeSH
• buněčné linie MeSH
• dusitany metabolismus   MeSH
• karbazoly aplikace a dávkování   farmakologie   MeSH
• lipopolysacharidy MeSH
• makrofágy metabolismus   účinky léků   MeSH
• myši MeSH
• oxid dusnatý metabolismus   MeSH
• propanolaminy aplikace a dávkování   farmakologie   MeSH
• regulace genové exprese enzymů účinky léků   MeSH
• signální transdukce účinky léků   MeSH
• synthasa oxidu dusnatého, typ II metabolismus   účinky léků   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• práce podpořená grantem MeSH