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

This study sought to evaluate whether consumption of polyphenol extract from Cognac (CPC) modulates platelet activation and cardiovascular reactivity in rats. Male Wistar rats were treated daily for 4 weeks by intra-gastric gavage receiving CPC at 80 mg/kg/day or vehicle (5 % glucose). Platelet adhesion and aggregation in response to different activators were assessed. Cardiac and vascular reactivity in response to various agonists as well as NO measurement by electron paramagnetic resonance technique were investigated in isolated heart and thoracic aorta. Oral administration of CPC decreased platelet aggregation induced by ADP but not by collagen. CPC did not affect adhesion to collagen. The chronotropic but not the inotropic response to isoprenaline was reduced without alteration of NO production in hearts from CPC-treated rats. CPC treatment did not affect ex vivo relaxation to acetylcholine nor NO content of rat aorta. CPC did not significantly alter the response to phenylephrine in aorta despite the participation of endothelial vasoconstrictor products. In summary, chronic treatment with CPC has no impact on ex vivo vascular and cardiac reactivity; however, it reduced heart work and platelet aggregation. These data suggest the existence of compounds in Cognac that may decrease the risk of coronary thrombosis and protect against some cardiac diseases.

• MeSH
• adenosindifosfát antagonisté a inhibitory   farmakologie   MeSH
• agonisté adrenergních beta-receptorů farmakologie   MeSH
• agregace trombocytů účinky léků   MeSH
• alkoholické nápoje analýza   MeSH
• aorta thoracica účinky léků   MeSH
• buněčná adheze účinky léků   MeSH
• elektronová paramagnetická rezonance MeSH
• fenoly farmakologie   MeSH
• flavonoidy farmakologie   MeSH
• isoprenalin antagonisté a inhibitory   farmakologie   MeSH
• kolagen metabolismus   MeSH
• krysa rodu Rattus MeSH
• myokard metabolismus   MeSH
• oxid dusnatý fyziologie   MeSH
• polyfenoly MeSH
• potkani Wistar MeSH
• srdce účinky léků   MeSH
• srdeční frekvence účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adenosindifosfát MeSH
• agonisté adrenergních beta-receptorů MeSH
• fenoly MeSH
• flavonoidy MeSH
• isoprenalin MeSH
• kolagen MeSH
• oxid dusnatý MeSH
• polyfenoly MeSH