Sex differences in response to chronic administration of Tacrolimus 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) is a potent immunosuppressive used to decrease occurrence of allograft rejection. The present study tested the hypothesis that there are sex differences in response to tacrolimus in SHR. Young male (YM, age 3 mos; n= 6) and young female (YF, aged 3 mos; n= 4–5) SHR received tacrolimus (0.25 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), but had no effect in females (Control: 132 ±3 mmHg vs. Tacrolimus‐treated: 133 ±2 mmHg). After the experiment, blood was taken and the numbers of CD4+ and CD8+ T cells in peripheral blood leukocytes (PBL) were measured by flow cytometry. The number of CD4+ T cells decreased by similar percentage in females (Control: 42 ±7 vs. Treated: 30 ±4% gated) and males (Control: 49 ±2 vs. Treated: 32 ±3% gated) treated with tacrolimus. However, tacrolimus treatment decreased the number of CD8+ by 72% in females (Control: 18 ±6 vs. Treated: 5 ±2% gated) and 40% in males (Control: 33 ±2 vs. Treated: 20 ±1% gated). The data show that in spite of similar reductions in CD4+ cells and greater reduction in CD8+ T cells, tacrolimus had no effect on MAP in females. In males, tacrolimus increased MAP despite decline in CD4+ and CD8+ T cells. Thus the contribution of CD4+ and CD8+ T cells in mediating the hypertension in male and female SHR is not clear.