The influence of gender on cardiac fibrosis induced by sympathetic stimulation

We examined the influence of sex steroids on cardiac effects of sympathetic agents in mice. The mice were divided into four groups: males, neutered males (N-males), females, and neutered females (N-females). Dobutamine (DOB; 2.5, 5.0, 10 microg/kg/min) or isoproterenol (ISO; 0.01, 0.02, 0.04 microg/kg/min) were given intravenously to compare the fractional shortening (FS). These mice received isoproterenol twice daily at a dose of 7.5 microg/g/day for 3 weeks. The rate of cardiac fibrosis was evaluated pathologically with Azan stain after 3 weeks of ISO. DOB and ISO significantly increased the FS in the male group, compared with other groups. There was no significant difference in FS between the female and N-female groups. Cardiac fibrosis significantly increased in the male group, compared with the N-male group. The female and N-female groups had increased cardiac fibrosis, compared with the male and N-male groups. These findings suggest that testosterone is one of the factors of modulation of the response to the sympathetic nervous system. Further study is needed to clarify the relationships between female sex steroids and cardiac fibrosis.