Relaxation induced by red wine polyphenolic compounds in rat pulmonary arteries:: lack of inhibition by NO-synthase inhibitor

Some red wine polyphenols exert nitric oxide (NO)-dependent relaxation in systemic arteries, following activation of endothelial NO synthase (eNOS). In this study, the effect of red wine polyphenols was determined in rat intrapulmonary arteries, and the effect of some of these compounds was compared with the responses obtained in rat aorta. In pulmonary arteries, red wine polyphenolic extract (> 300 mu g/mL) exerted relaxation that was not inhibited by the NOS inhibitor N-omega-nitro-L-arginine methylester (L-NAME) or endothelium removal. Among the several fractions obtained from the extract, the one enriched with anthocyanins was less active than fractions containing non-anthocyanins. Among the latter, the most active for relaxing pulmonary arteries was the one enriched in the stilbene derivative trans-resveratrol (relaxation for concentration >10 mu g/mL). Trans-piceid, the glucoside derivative of trans-resveratrol, was almost inactive. Trans-resveratrol-induced relaxation, as well as relaxation to the anthocyanin delphinidin, was L-NAME-insensitive in pulmonary arteries. In aorta, trans-resveratrol and trans-piceid exerted similar effects to those in pulmonary arteries that were also not inhibited by L-NAME. However, red wine polyphenolic extract and delphinidin induced relaxation of aorta at much lower concentrations (about 10 mu g/mL) than in pulmonary arteries, and their effects were inhibited by L-NAME. These data show differences between small intrapulmonary arteries and systemic conductance arteries in their responses to red wine polyphenols, the major difference being that the relaxant effect of these compounds is not blunted by NOS inhibitor in pulmonary arteries. They suggest that red wine polyphenols act directly on smooth muscle to promote pulmonary artery relaxation.