Introduction: Our previous studies demonstrated that T cells modulate the development of angiotensin II (Ang II)-stimulated hypertension in a sex-specific manner; male T cells augment the magnitude of hypertension while female T cells do not. After adoptive transfer of male T cells into male recombinant activation gene-1 null mice (Rag-1-/–M), the mean arterial pressure and the frequency of the prohypertensive CD3+, interleukin-17+ T cell subset was 20 mm Hg and 2.25X higher, respectively, than after adoptive transfer of female T cells. Approach: To determine if this sex-specific effect of T cells is due to intrinsic sex chromosome (XX vs XY) differences between male and female T cells or to sex differences in exposure to gonadal hormones, Rag-1-/–M mice were exposed to 800 rads (8 Gy) using a 137 Cs irradiator. Seven days prior to irradiation, Baytril (0.17 mg/mL) was added to the sterile drinking water of the recipient Rag-1-/–M mice and the mice were maintained on this antibiotic supplemented water for an additional two weeks after irradiation to prevent infections. Four to six hours after irradiation, the mice received (via retro-orbital injection) 5 x 107 (in 0.15 mL phosphate buffered saline) unfractionated bone marrow (BM) cells isolated from the femur and tibia of wild type male or female (WT-M or WT-F) mice. Radiotransmitters were implanted four weeks later and after a stable baseline was established, an osmotic minipump containing Ang II (490 ng/ml/min) was inserted followed by continuous measurement of mean arterial pressure for two weeks by telemetry. Results: We found no difference in the magnitude of hypertension induced by Ang II infusion between BMFgRag1-/–M (143±4.1 mm Hg; n=6) and BMMgRag1-/–M (149±4.7 mm Hg; n=6) mice or in the frequency of the CD3+, interleukin 17+ T cell subset [BMFgRag1-/–M, 2.36 ± 0.21% vs. BMMgRag1-/–M, 2.06 ± 0.51; n=6/group]. Conclusions: Sex-specific T cell modulation of blood pressure is due to gonadal hormone effects on T cell expansion including the prohypertensive CD3+, interleukin 17+ T cell subset, rather than intrinsic sex chromosome differences between male and female T cells.
Physiology 2016 (Dublin, Ireland) (2016) Proc Physiol Soc 37, SA089
Research Symposium: Sex differences in hypertension: Immune mechanisms underlying resilience and susceptibility
K. Sandberg1, X. Liu1, X. Wu1, H. Ji1
1. Georgetown University, Washington Dc, Washington, United States.
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Where applicable, experiments conform with Society ethical requirements.