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 Ca2+-free medium, RWPC1 but not Provinols treatment induced an increase in noradrenaline-induced contraction. After depletion of intracellular Ca2+ stores by noradrenaline in Ca2+-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 Ca2+-ATPase, thapsigargin, significantly reduced noradrenaline-induced contraction in Ca2+-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, oxadiazoloquinoxaline or the protein kinase G inhibitor, 8-Bromoguanosine-3′-5-cyclic monophosphorothioate, 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.