DAILY RED WINE CONSUMPTION IMPROVES VASCULAR FUNCTION IN YOUNG HEALTHY WOMEN, PROPABLY BY AN ENDOTHELIUM-DEPENDENT NITRIC OXIDE-SOLUBLE GUANYLYL CYCLASE - MEDIATED PATHWAY: PP.6.236

Abstract

Objective: Polyphenols in red wine are believed to improve endothelial function. We investigated whether daily consumption of red wine improves in vivo vascular function. After ingestion, red wine components are present for some time in the circulation. Therefore, we also studied whether incubation of porcine coronary arteries (PCAs) with red wine extract (RWE) improves vascular function in vitro. Methods: Eighteen young healthy women drank red wine daily for three weeks. Vascular function was evaluated as forearm blood flow (FBF). For the in vitro study, PCAs were suspended in organ baths in the absence or presence of the NOS inhibitor L-NAME and/or the soluble guanylyl cyclase (sGC) inhibitor ODQ. In a number of vessels, the endothelium was removed. Concentration-response curves to RWE were constructed following preconstriction with U46619. The effect of RWE incubation was studied by quantifying bradykinin- and S-nitroso-N-penicillamine (SNAP)- induced vasorelaxation following acute (0.5 hour and 2 hours) or chronic (16 hours) pre-incubation with RWE. Results: Acetylcholine-induced, endothelium-dependent and sodium nitroprusside-induced, endothelium-independent FBF increases were enhanced after three weeks of red wine consumption, but not acutely after one unit of red wine (corresponding with 10 g of alcohol). In vitro, RWE fully relaxed U46619-preconstricted PCAs. This effect was endothelium-dependent and strongly reduced by L-NAME and ODQ. Acute pre-incubation with RWE blocked bradykinin-induced relaxation, and this effect tended to disappear upon chronic pre-incubation. Similarly, acute, but not chronic, RWE pre-incubation diminished the SNAP-induced response. Conclusions: In vitro, RWE causes endothelium-dependent, NO- and sGC-mediated relaxations of coronary arteries. Pre-incubation with RWE reduces the bradykinin- and SNAP-induced relaxation, possibly via sGC inactivation induced by the high levels of NO generated by RWE. This effect disappears upon prolonged pre-incubation. These data are in line with our in vivo results, where the lack of an acute effect of red wine may be attributed to sGC inactivation, whereas the improved effect after prolonged wine exposure may reflect sGC upregulation and/or structural vascular alterations.