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Vasorelaxant effects of grape polyphenols in rat isolated aorta. Possible involvement of a purinergic pathway
Author(s) -
Mendes Anne,
Desgranges Claude,
Chèze Catherine,
Vercauteren Joseph,
Freslon JeanLouis
Publication year - 2003
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1046/j.1472-8206.2003.00198.x
Subject(s) - chemistry , apyrase , purinergic receptor , methylene blue , catechin , polyphenol , biochemistry , stereochemistry , enzyme , adenosine , antioxidant , photocatalysis , catalysis
The purpose of this study was to investigate the mechanism of the vascular relaxation produced by polyphenolic substances from red wine, with a particular focus on the possible involvement of purinoceptors. With this aim, relaxing responses induced by procyanidin from grape seeds (GSP), anthocyanins, catechin and epicatechin were assessed in rat isolated aortic rings left intact (+E) or endothelium‐denuded (−E). In preparations precontracted with noradrenaline, incubation with N G ‐nitro‐ l ‐arginine methyl ester (100 μ m , 30 min) fully inhibited the GSP‐induced relaxations. Concentration–effect curves to these substances (from 10 −7 to 10 −1 g/L) were determined in depolarized (60 m m KCl) preparations in control condition, after incubation with reactive blue 2 (an antagonist of P2Y purinoceptors, 30 μ m ), with apyrase (an enzyme which hydrolyses ATP and ADP, 0.8 U/mL) or with α , β ‐methylene ATP (an inhibitor of ecto ATPases, 10 μ m ). In (+E) rings, relaxations (expressed as percentage of initial contraction) were 41 ± 2 and 37 ± 3 for GSP and anthocyanins, respectively. Only modest relaxations ( ca. 10%) were observed in (−E) rings, as it was the case for catechin and epicatechin in (±E) rings. Reactive blue 2 or apyrase inhibited the GSP‐ and anthocyanin‐induced relaxations in (+E) rings, while α , β ‐methylene ATP shifted to the left the relaxation curves obtained with GSP. These data confirm that modest relaxations observed with catechin and epicatechin are not endothelium‐dependent but that GSP and anthocyanins induce a relaxing effect, which is related to the integrity of the endothelium and the synthesis and release of nitric oxide (NO). Furthermore, the inhibition by apyrase and the increase by ecto‐ATPase inhibition of the GSP‐ and anthocyanin‐induced relaxation suggest that these substances could act via an initial release of nucleotides, which in turn could activate P2Y 1 and/or P2Y 2 purinoceptors of endothelial cells, trigger the synthesis and release of NO and then lead to relaxation.