Wine Polyphenols Stimulate Superoxide Anion Production to Promote Calcium Signaling and Endothelial-Dependent Vasodilatation

J. DUARTE¹, E. ANDRIAMBELOSON, M. DIEBOLT, R. ANDRIANTSITOHAINA

Laboratoire de Pharmacologie et Physico-Chimie des Interactions Cellulaires et Moléculaires, Université Louis Pasteur de Strasbourg, CNRS, Faculté de Pharmacie, Illkirch, France and ¹Department of Pharmacology, Faculty of Pharmacy, University of Granada, Granada, Spain

Received December 4, 2003
Accepted April 29, 2004



Summary
The present study was aimed to evaluate the mechanisms involved in the vasorelaxant effects of red wine polyphenol compounds (RWPC) in small mesenteric rat arteries. RWPC produce relaxation in small mesenteric arteries. This relaxant effect was abolished by endothelial denudation, NO-synthase blockade with L-NAME and partial depolarization with KCl or L-NAME plus KCl. Incubation with the reactive oxygen species scavenger, superoxide dismutase (SOD) plus catalase, or inhibition of NAD(P)H-dependent oxidoreductases with diphenyleneiodonium also inhibited RWPC induced vascular relaxation. Application of RWPC elicited a transient increase in intracellular calcium concentration ([Ca2+]i) in bovine aortic endothelial cells (BAEC), which was attenuated by a mixture of SOD and catalase. Incubation of BAEC with RWPC increased the SOD inhibitable production of O2-. These results suggest the involvement of O2- in the [Ca2+]i increase evoked by RWPC, leading to the activation of enzymes involved in the release of endothelial relaxant factors and subsequent vasodilatation of resistance arteries.


Key words
Red wine polyphenol compounds • Nitric oxide • Calcium • Superoxide anions • Endothelium • Mesenteric artery