Blockade by Nanomolar Resveratrol of Quantal Catecholamine Release in Chromaffin Cells

Abstract

The cardiovascular protecting effects of resveratrol, an antioxidant polyphenol present in grapes and wine, have been attributed to its vasorelaxing effects and to its anti-inflammatory, antioxidant, and antiplatelet actions. Inhibition of adrenal catecholamine release has also been recently implicated in its cardioprotecting effects. Here, we have studied the effects of nanomolar concentrations of resveratrol on quantal single-vesicle catecholamine release in isolated bovine adrenal chromaffin cells. We have found that 30 to 300 nM concentrations of resveratrol blocked the acetylcholine (ACh) and high K ϩ -evoked quantal catecholamine release, amperometrically measured with a carbon fiber microelectrode. At these concentrations, resveratrol did not affect the whole-cell inward currents through nicotinic receptors or voltage-dependent sodium and calcium channels, neither the ACh-or K ϩ -elicited transients of cytosolic Ca 2ϩ . Blockade by nanomolar resveratrol of secretion in ionomycin-or digitonin-treated cells suggests an intracellular site of action beyond Ca 2ϩ -dependent exocytotic steps. The fact that nanomolar resveratrol augmented cGMP is consistent with the view that resveratrol could be blocking the quantal secretion of catecholamine through a nitric oxide-linked mechanism. Because this effect occurs at nanomolar concentrations, our data are relevant in the context of the low circulating levels of resveratrol found in moderate consumers of red wines, which could afford cardioprotection by mitigating the catecholamine surge occurring during stress.

Plasmalemmal sodium-calcium exchanger shapes the calcium and exocytotic signals of chromaffin cells at physiological temperature

“…3B). As previously observed (12) in the present study, we also found that BCCs rarely exhibited spontaneous single exocytotic events; this made easier the analysis of the net responses elicited by 30K ϩ . Thus the net bulk secretion (the cumulative sum of the areas of all spikes produced within a DP, the so-called quantal content or Q amp ) and the total number of spikes, considerably differed at the Data are means Ϯ SE and were pooled and analyzed from the peak Ca 2ϩ current (ICa) obtained at Ϫ10 mV, shown in Fig.…”

Trans‐resveratrol simultaneously increases cytoplasmic Ca2+ levels and nitric oxide release in human endothelial cells

“…Bearing in mind that t-Resv has been reported to have beneficial effects in the cardiovascular system through a NO-dependent mechanism [52,53], and assuming that t-Resv exhibits similar behaviour in humans in vivo, we suggest that the endothelial NO release described here may be partially involved in these effects. However, it is important to note that the effects described in this study were obtained with concentrations of t-Resv considerably higher than those measured in human plasma after normal dietary intake [54,55]. This suggests that the potential beneficial effect of resveratrol on the vascular endothelium will not be achieved after its dietary consumption, such as a moderate wine intake, and that a pharmacological intervention could be necessary to reach higher plasma levels.…”

Resveratrol’s Impact on Vascular Smooth Muscle Cells Hyporeactivity: The Role of Rho-Kinase Inhibition

“…e hyporeactivity was confirmed by a significant increase in the EC50 coefficient value in the study group and by lower maximal pressure values. Fernandez-Morales et al observed similar effects at nanomolar concentrations of resveratrol [13]. Kline and Karpiński's [14] study showed that resveratrol also depends on nonreceptor vasorelaxant mechanisms.…”