We recently reported that in vitro Cognac polyphenolic compounds (CPC) induce NO-dependent vasorelaxant effects and stimulate cardiac function. In the present study, we aim to investigate the effect of CPC on both nitric oxide (NO) and superoxide anions (O(2)(-)) production in cultured human endothelial cells. In addition, its effect on the bradykinin (BK)-induced NO production was also tested. The role and sources of O(2)(-) in the concomitant effect of BK plus CPC were pharmacologically determined. NO and O(2)(-) signals were measured using electron paramagnetic resonance technique using specific spin trappings. Both, CPC and BK induced an increase in NO production in human endothelial cells. The combination of both further enhanced NO release. The capacity of CPC plus BK to increase NO signal was blunted by the NO synthase inhibitor, N(G)-nitro-L-arginine methyl ester, and was enhanced in the presence either of superoxide dismutase or catalase. Moreover, CPC plus BK response was greater after inhibition of either NADPH oxidase by apocynin or xanthine oxidase by allopurinol but it was not affected by rotenone. CPC did not affect O(2)(-) level either alone or after its increase upon lipopolysaccharide treatment. Finally, the capacity of BK alone to increase NO was enhanced either by apocynin or allopurinol. Altogether, these data demonstrate that CPC is able to directly increase NO production without affecting O(2)(-) and enhances the BK-induced NO production in human endothelial cells. The data highlight the ability of BK to stimulate not only NADPH oxidase- but also xanthine oxidase-inhibitor sensitive mechanisms that reduce its efficiency in increasing NO either alone or in the presence of CPC. These results bring pharmacological evidence for vascular protection by CPC via its potentiating effect of BK response in terms of endothelial NO release.

• MeSH
• alkoholické nápoje * analýza   MeSH
• bradykinin metabolismus   MeSH
• buněčné linie MeSH
• endoteliální buňky účinky léků   enzymologie   metabolismus   MeSH
• fenoly analýza   farmakologie   MeSH
• flavonoidy analýza   farmakologie   MeSH
• inhibitory enzymů farmakologie   MeSH
• katalasa metabolismus   MeSH
• lidé MeSH
• lipopolysacharidy farmakologie   MeSH
• NADPH-oxidasy antagonisté a inhibitory   metabolismus   MeSH
• oxid dusnatý metabolismus   MeSH
• polyfenoly MeSH
• superoxiddismutasa metabolismus   MeSH
• superoxidy metabolismus   MeSH
• synthasa oxidu dusnatého antagonisté a inhibitory   metabolismus   MeSH
• upregulace MeSH
• xanthinoxidasa antagonisté a inhibitory   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• bradykinin MeSH
• fenoly MeSH
• flavonoidy MeSH
• inhibitory enzymů MeSH
• katalasa MeSH
• lipopolysacharidy MeSH
• NADPH-oxidasy MeSH
• oxid dusnatý MeSH
• polyfenoly MeSH
• superoxiddismutasa MeSH
• superoxidy MeSH
• synthasa oxidu dusnatého MeSH
• xanthinoxidasa MeSH