Gender differences in age-related endothelial function in aorta

We investigated the gender differences on the endothelial function in aortas from aged mice. Acetylcholine (ACh)-induced relaxations in aortic rings were impaired in the old male mice group compared with age matched female and male-young mice. Sodium nitroprusside (SNP)-induced relaxations were not altered between these groups. To exzmine superoxide generation by NBT reduction and the expression of 3-nitrotyrosine, a marker of ONOO-, were increased in aortas from male-old mice. The expressions of Cu/Zn-SOD and EC-SOD were increased in aorta from female young and old mice. SOD activities were lower in the male old mice than female old mice. Endothelium-dependent relaxations to ACh (10(-7)M) were attenuated in the presence of NADH (10(-5)M), dietyldithiocarbamate (DDC; 10(-3)M), an SOD inhibitor, in the aortas from male-young, female-young and female-old mice. On the other hand, in the aortas from male-old mice impaired relaxations by ACh were increased in the presence of tempol (10(-4)M), an SOD mimetic, but they were altered by preincubated with NADH or DDC. Superoxide generation to ACh in aortas was increased in the presence of NADH and DDC in the aorta from male-young, female-young and female-old mice. In the aortas from male-old mice, superoxide generation to ACh stimulated aorta was decreased in the presence of tempol. These results suggest that an impaired endothelium-dependent relaxation in aged male mouse aorta is due to excess amount of superoxide anions.