Role of estrogens and age in flow-mediated outward remodeling of rat mesenteric resistance arteries.

International audienceIn resistance arteries a chronic increase in blood flow induces hypertrophic outward remodeling. This flow-mediated remodeling (FMR) is absent in male rats aged 10 months and more. As FMR depends on estrogens in 3-month old female rats, we hypothesized that it might be preserved in 12-month old female rats. Blood flow was increased in vivo in mesenteric resistance arteries after ligating side arteries in 3- and 12-month old male and female rats. After 2 weeks, high (HF) and normal flow (NF) arteries were isolated for in vitro analysis. Arterial diameter and cross sectional area increased in HF, compared to NF arteries, in 3-month old male and female rats. In 12-month old rats, diameter increased only in female rats. Endothelial NO-synthase expression and endothelium-mediated relaxation were higher in HF than in NF arteries in all groups. ERK1/2 phosphorylation, NADPHoxidase subunits expression level and arterial contractility to KCl and to phenylephrine were greater in HF than in NF vessels in 12-month old male rats only. Ovariectomy in 12-month old female rats induced a similar pattern with an increased contractility without diameter increase in HF arteries. Treatment of 12-month old male rats and ovariectomized female rats with hydralazine, the antioxidant TEMPOL or the angiotensin II type 1 receptor blocker candesartan restored HF-remodeling and normalized arterial contractility in HF vessels. Thus, we found that FMR of resistance arteries remains efficient in 12-month old female rats compared to age-matched male rats. A balance between estrogens and vascular contractility might preserve FMR in mature female rats