Abstract
ObjectivesChronic increases in blood flow in resistance arteries induce outward remodeling associated with increased wall thickness and endothelium-mediated dilatation. This remodeling is essential for collateral arteries growth following occlusion of a large artery. As estrogens have a major role in this remodeling, we hypothesized that resveratrol, described as possessing phytoestrogen properties, could improve remodeling in ovariectomized rats.MethodsBlood flow was increased in vivo in mesenteric arteries after ligation of adjacent arteries in 3-month old ovariectomized rats treated with resveratrol (5 or 37.5 mg/kg per day: RESV5 or RESV37.5) or vehicle. After 2 weeks arterial structure and function were measured in vitro in high flow (HF) and normal flow (NF) arteries isolated from each rat.ResultsArterial diameter was greater in HF than in NF arteries in ovariectomized rats treated with RESV5 or RESV37.5, not in vehicle-treated rats. In mice lacking estrogen receptor alpha diameter was equivalent in HF and NF arteries whereas in mice treated with RESV5 diameter was greater in HF than in NF vessels. A compensatory increase in wall thickness and a greater phenylephrine-mediated contraction were observed in HF arteries. This was more pronounced in HF arteries from RESV37.5-treated rats. ERK1/2 phosphorylation, involved in hypertrophy and contraction, were higher in RESV37.5-treated rats than in RESV5- and vehicle-treated rats. Endothelium-dependent relaxation was greater in HF than in NF arteries in RESV5-treated rats only. In HF arteries from RESV37.5-treated rats relaxation was increased by superoxide reduction and markers of oxidative stress (p67phox, GP91phox) were higher than in the 2 other groups.ConclusionResveratrol improved flow-mediated outward remodeling in ovariectomized rats thus providing a potential therapeutic tool in menopause-associated ischemic disorders. This effect seems independent of the estrogen receptor alpha. Nevertheless, caution should be taken with high doses inducing excessive contractility and hypertrophy in association with oxidative stress in HF arteries.
Highlights
The arterial tree has an important plasticity, which allows adapting to continuous changing conditions
Blood flow was increased in vivo in mesenteric arteries after ligation of adjacent arteries in 3-month old ovariectomized rats treated with resveratrol (5 or 37.5 mg/kg per day: resveratrol 5.0 mg/kg (RESV5) or RESV37.5) or vehicle
Arterial diameter was greater in high flow (HF) than in normal flow (NF) arteries in ovariectomized rats treated with RESV5 or RESV37.5, not in vehicle-treated rats
Summary
The arterial tree has an important plasticity, which allows adapting to continuous changing conditions. Resistance arteries play a major role in the control of local blood flow to organs and their dysfunction is associated to the major vascular diseases [3]. They are sensitive to chronic changes in the hemodynamic environment and undergo rapid structural and functional remodeling [4,5,6]. Chronic increases in blood flow (shear stress) induce outward remodeling in resistance arteries associated with a functional remodeling mainly characterized by improvement of endothelium (NO)-dependent dilation [7,8,9,10,11,12]. High-flow-mediated outward remodeling allows collateral arteries growth and it is essential in post-ischemic revascularization besides angiogenesis [14, 15]
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