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 (O2 -) 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 O2 - in the concomitant effect of BK plus CPC were pharmacologically determined. NO and O2 - 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, NG-nitro-Larginine 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 O2 - 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 O2 - 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.
- Klíčová slova
- Polyphenols, Reactive oxygen species, Endothelial cells,
- MeSH
- alkoholické nápoje analýza MeSH
- bradykinin metabolismus MeSH
- buněčné linie MeSH
- endoteliální buňky enzymologie metabolismus účinky léků MeSH
- fenoly analýza farmakologie MeSH
- financování organizované 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
- 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
Microparticles are small fragments of the plasma membrane released by activated and/or apoptotic cells. In theory, all type of cells can shed microparticles representing a physiological process in the cell life. Mainly, microparticles generation has been studied in different cardiovascular pathologies due to the facility to obtain blood samples from individuals. Although microparticles have been considered as simply markers of several diseases, in the last decade, several studies support the hypothesis that they participate in the regulation of the cardiovascular system function by carrying biological messages between cells. Among the effects of microparticles, recent data show that they can be implicated in the modulation of neovascularization, an essential function of cells from cardiovascular system during either ischemic diseases or cancer development. Whereas during pathologies associated with ischemia an increase of neovascularization may have beneficial effects, anti-angiogenic strategies represent new approaches for manipulation of tumor development. Here, we give an overview of the mechanisms and factors involved in neovascularization, and finally, we look at the role and the consequences of the modulation of this process by microparticles in pathological situations.
- MeSH
- buněčná membrána metabolismus MeSH
- endoteliální buňky metabolismus MeSH
- financování organizované MeSH
- fyziologická neovaskularizace MeSH
- ischemie metabolismus patofyziologie MeSH
- lidé MeSH
- nádory krevní zásobení metabolismus patofyziologie MeSH
- patologická angiogeneze metabolismus patofyziologie MeSH
- transportní vezikuly metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH