From the Department of Physiology (A.J.T., J.C.S.) and Department of Oral Biology (B.B.), Georgia Regents University, Augusta.
Hypertension. 2014 Sep;64(3):557-64. doi: 10.1161/HYPERTENSIONAHA.114.03512. Epub 2014 Jun 9.
Female spontaneously hypertensive rats (SHR) have more regulatory T cells (Tregs) in their kidneys than males. The goal of this study was to determine the impact of blood pressure (BP) on the renal immune profile. We hypothesize that increases in BP promote a proinflammatory renal T cell and cytokine profile in SHR, although females will have greater hormone-dependent increases in Tregs and males will have greater increases in Th17 cells. Renal T cell and cytokine profiles were assessed in male and female Wistar-Kyoto rats and male and female SHR treated with vehicle or hydrochlorothiazide and reserpine (HCTZ) from 6 to 12 (6-HCTZ) or 11 to 13 weeks of age (2-HCTZ). Regardless of sex, SHR had a more proinflammatory renal immune profile than Wistar-Kyoto rats. 6-HCTZ attenuated age-related increases in BP and 2-HCTZ reversed hypertension compared with vehicle-treated SHR. Neither 6-HCTZ nor 2-HCTZ altered CD3(+), CD4(+), or CD8(+) T cells in either sex. Both treatments decreased Tregs only in female SHR abolishing sex differences in Tregs. 6-HCTZ has no impact on Th17 cells in either sex and 2-HCTZ had a minimal impact on renal Th17 cells. To further assess mechanisms mediating sex differences in the renal immune profile, male and female SHR were gonadectomized to determine the impact of sex hormones. Gonadectomy increased proinflammatory markers in both sexes, suggesting that both male and female sex hormones are anti-inflammatory. In conclusion, BP contributes to sex differences in the renal T-cell profile of SHR; female SHR increase renal Tregs in response to increases in BP.
雌性自发性高血压大鼠（SHR）的肾脏中调节性 T 细胞（Tregs）多于雄性。本研究的目的是确定血压（BP）对肾脏免疫谱的影响。我们假设，BP 的升高会促进 SHR 肾脏中促炎的 T 细胞和细胞因子谱的形成，尽管女性的 Tregs 会因激素依赖性增加而增加，而男性的 Th17 细胞会增加更多。评估了雄性和雌性 Wistar-Kyoto 大鼠以及雄性和雌性 SHR 的肾脏 T 细胞和细胞因子谱，这些大鼠在 6 至 12 周（6-HCTZ）或 11 至 13 周（2-HCTZ）龄时接受 vehicle 或氢氯噻嗪和利血平（HCTZ）治疗。无论性别如何，SHR 的肾脏免疫谱均比 Wistar-Kyoto 大鼠更具促炎作用。6-HCTZ 可减轻与年龄相关的 BP 升高，而 2-HCTZ 与 vehicle 治疗的 SHR 相比可逆转高血压。6-HCTZ 和 2-HCTZ 均未改变任何性别 CD3(+)、CD4(+)或 CD8(+)T 细胞。两种治疗方法均仅降低了雌性 SHR 的 Tregs，消除了 Tregs 上的性别差异。6-HCTZ 对任何性别中的 Th17 细胞均无影响，而 2-HCTZ 对肾脏 Th17 细胞的影响很小。为了进一步评估介导 SHR 肾脏免疫谱性别差异的机制，对雄性和雌性 SHR 进行了性腺切除术，以确定性激素的影响。性腺切除术增加了两性的促炎标志物，表明雄性和雌性性激素均具有抗炎作用。总之，BP 导致 SHR 肾脏 T 细胞谱的性别差异；雌性 SHR 会因 BP 升高而增加肾脏 Tregs。
