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Sex differences in response to chronic administration of Tacrolimus in spontaneously hypertensive rats
Author(s) -
Moulana Mohadetheh,
Wallace Kedra,
Lima Roberta,
Zhang Huimin,
Mathbout Mohammad,
LaMarca Babbette,
Reckelhoff Jane
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.lb837
Subject(s) - tacrolimus , medicine , cd8 , immune system , blood pressure , endocrinology , lymphocyte subsets , immunology , transplantation
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.