This study explored the possible involvement of AT(2) receptor stimulation in the age-related gender difference in vascular remodeling of mouse femoral artery induced by cuff placement. In the young adult group of wild-type mice (10 weeks of age), the increase in DNA synthesis, neointimal formation, expression of chemokines, and superoxide anion production in the injured femoral artery were smaller in female than in male mice. These gender differences were smaller in the aged group (50-55 weeks of age) of wild-type mice, because vascular responses of female mice in the aged group were stronger than those in the young group. Treatment with 17β-estradiol attenuated vascular remodeling in aged female mice. AT(2) receptor expression in the injured artery was higher in female than in male in the young group. AT(2) receptor expression in the injured artery of female mice was lower in the aged group than in the young group. Lack of AT(2) receptor increased neointimal formation in the aged group and reduced the inhibitory action of 17β-estradiol in aged female mice. Our findings suggest a possibility that the change in AT(2) receptor stimulation by aging might be involved in the response to estrogen and improvement of vascular remodeling in the aged female group.
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