0223 : Dual effect of resveratrol on flow-mediated outward hypertrophic remodeling in ovariectomized rat mesenteric resistance arteries

Resistance arteries control local blood flow. Chronic increases in blood flow in RA occur in growth, pregnancy, exercising as well as to compensate ischemia and induce outward hypertrophic remodeling associated with improved endothelium dilation. As estrogens have a key role in flow-mediated remodeling, we hypothesized that resveratrol, suggested to act as phytoestrogen, may improve flow-mediated remodeling in ovariectomized rats. Blood flow was increased in vivo in one mesenteric resistance artery without other changes in pressure or circulating factors in three-month old ovariectomized female rats treated with resveratrol (5 or 37.5mg/kg per day in osmotic minipumps: RESV5 or RESV37.5) or solvent (DMSO). After 2 weeks arterial structure and function were measured in vitro. Arterial diameter increased in high flow (HF) compared to normal flow (NF) arteries in ovariectomized rats treated with RESV5 or RESV37.5, not in control rats. Hypertrophy in HF arteries occurred in the 3 groups but was greater in RESV37.5-treated rats so that wall / lumen ratio was elevated in this group. ERK1/2 activation, involved in flow-mediated hypertrophy was greater in RESV37.5-treated rats than in RESV5 – and DMSO-treated rats. RESV5, not RESV37.5, improved L-NAME sensitive arterial relaxation. eNOS expression level was equivalent in HF and NF vessels in all groups animals. Markers of oxidative stress (p67phox, GP91phox) were greater in arteries of RESV37.5-treated rats than in RESV5 – and solvent-treated rats. They were also higher in HF arteries in RESV37.5-treated rats. Thus, although resveratrol improved flow-mediated outward hypertrophic remodeling in OVX rats, the high dose induced oxidative stress and hypertrophy.