Wine polyphenols modulate calcium handling in rat aorta: involvement of nitric oxide pathway.
The effects of short-term oral administration of red wine polyphenolic compounds (RWPCs) on blood pressure and vascular reactivity were investigated in rats. The consequence of RWPCs treatment on agonist-induced contractility of rat aorta with respect to Ca2+ handling was assessed, by examining both intracellular Ca2+ store and extracellular Ca2+ influx components of the response. Rats were treated daily for 7 days by intragastric administration of either 5% glucose, or RWPCs (20 mg/kg) [from two different sources, i.e. Provinols (SFD, Vallont Pont d'Arc, France) and RWPC1 (INRA, Montpellier, France)]. Administration of these compounds produced a decrease in systolic blood pressure. The consequence of RWPCs treatment on vascular smooth muscle was investigated in rat aorta without endothelium exposed to noradrenaline. In Ca(2+)-free medium, RWPC1 but not Provinols treatment induced an increase in noradrenaline-induced contraction. After depletion of intracellular Ca2+ stores by noradrenaline in Ca(2+)-free medium, addition of CaCl2 in the continuous presence of agonist induced an increase in contraction, which was not significantly different between control, Provinols- and RWPC-treated rats. The presence of an inhibitor of sarcoplasmic reticulum Ca(2+)-ATPase, thapsigargin, significantly reduced noradrenaline-induced contraction in Ca(2+)-free medium in RWPCs-treated aorta, as compared to that of control. Interestingly, the inhibitory effect of thapsigargin on the response linked to the release of Ca2+ from internal stores in RWPCs-treated vessels was completely prevented in the presence of NO-synthase inhibitor, L-nitro arginine methyl ester, the inhibitor of guanylyl cyclase, oxadiazolo-quinoxaline or the protein kinase G inhibitor, 8-Bromoguanosine-3'-5-cyclic mono-phosphorothioate, Rp isomer. These results suggest that short-term administration of RWPCs in rats induced subtle alteration of thapsigargin-sensitive component of agonist-induced contraction in rat aorta linked to Ca2+ release from intracellular store. Calcium release from intracellular stores sensitive to thapsigargin was implicated in this mechanism. The prevention of the inhibitory effect of thapsigargin by the inhibitors of NO/cyclic guanosine monophosphate pathway after RWPCs treatment highlights the role of NO in this phenomenon.
Diebolt
Myriam
M
Pharmacologie et Physicochimie des Interactions Cellulaires et Moléculaires, CNRS UMR 7034, 67 route du Rhin, Faculté de Pharmacie, 67401 Illkirch, France.
Andriantsitohaina
Ramaroson
R
D000284:Administration, Oral; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D010636:Phenols / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D019284:Thapsigargin / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014920:Wine
D004791:Enzyme Inhibitors; D010636:Phenols; D014662:Vasoconstrictor Agents; D009569:Nitric Oxide; D019284:Thapsigargin; D017869:Cyclic GMP-Dependent Protein Kinases; D006162:Guanylate Cyclase; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine