Abstract 158: Sex Differences in Response to Chronic Administration of Immunosuppressive Agents in Spontaneously Hypertensive Rats
Hypertension in male spontaneously hypertensive rats (SHR) is thought to be mediated in part by enhanced immune function. Tacrolimus (FK-506) and Mycophenolate Mofetil (MMF); potent immunosuppressive agents are widely used for the prevention of graft rejection in organ transplantation. Tacrolimus inhibits proliferation of T cells, whereas MMF inhibits proliferation of T cells, B cells and monocytes. However, the impact of the drug on the cardiovascular system of different sexes is unknown. The present study tested the hypothesis that there are sex differences in response to FK-506 and/or MMF in SHR. Young male (YM, age 3 mos; n= 6) and young female (YF, aged 3 mos; n= 6) SHR received tacrolimus (0.25 mg/kg/day i.p. for 14 d) and (YM, age 3 mos; n= 6) and young female (YF, aged 3 mos; n= 6) SHR received MMF (20 mg/kg/day i.p.) for 14 d. Rats were implanted with radiotelemeters and mean arterial pressure (MAP) was measured chronically. Tacrolimus increased MAP in males (Control: 143 ±3 mmHg vs. Tacrolimus-treated: 163 ±4 mmHg, p=S, p<0.05), but had no effect in females (Control: 132 ±3 mmHg vs. Tacrolimus-treated: 133 ±2 mmHg, p=NS). In contrast, Mycophenolate Mofetil significantly reduced MAP in both males (Control: 153 ±2 mmHg vs. MMF-treated: 140 ± 2 mmHg; p <0.05), and females (Control: 128 ±2 mmHg vs. MMF-treated: 114 ±2 mm Hg, p<0.05). These data suggest that immunosupproessive drugs may have different effects in men and women.
- © 2012 by American Heart Association, Inc.