Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital, McGill University, Montreal, Quebec, Canada.
Am J Physiol Heart Circ Physiol. 2010 Mar;298(3):H938-44. doi: 10.1152/ajpheart.00707.2009. Epub 2009 Dec 31.
Immune cells have been implicated in the pathogenesis of hypertension. We hypothesized that under the influence of chromosome (chr)2, T lymphocytes contribute to vascular inflammation in genetic salt-sensitive hypertension. Normotensive (Brown Norway), hypertensive (Dahl salt-sensitive), and consomic rats (SSBN2; in which chr2 has been transferred from Brown Norway to Dahl rats) were studied. Systolic blood pressure, measured by tail cuff, and aortic preproendothelin mRNA, measured by quantitative RT-PCR, were elevated in Dahl rats compared with Brown Norway rats and were reduced in SSBN2 rats compared with Dahl rats (P < 0.01). Compared with Brown Norway rats, Dahl rats exhibited increased inflammatory markers and mediators such as nuclear translocation of the aortic p65 subunit of NF-kappaB as well as VCAM-1, ICAM-1, chemokine (C-C motif) receptor 5, and CD4 mRNA, all of which were reduced in SSBN2 rats. Aortic CD8 mRNA was equally increased in Dahl and SSBN2 rats relative to Brown Norway rats. CD4(+) T cell infiltration in the aorta of SSBN2 rats was reduced compared with Dahl rats, whereas the aortic protein expression of Foxp3b and immunosuppressors transforming growth factor (TGF)-beta(1) and IL-10, the three markers associated with the regulatory T cell lineage, were enhanced in SSBN2 rats. Activation in vitro of T cells demonstrated that CD4(+)CD25(+) and CD8(+)CD25(+) cells (Tregs) produce IL-10 in SSBN2 rats. Thus, increased vascular inflammatory responses and hypertension in a genetic salt-sensitive hypertensive rodent model are reduced by transfer of chr2 from a normotensive strain, and this is associated with enhanced levels of immunosuppressive mediators.
免疫细胞已被牵连到高血压的发病机制中。我们假设，在染色体 2 的影响下，T 淋巴细胞可能会导致遗传性盐敏感高血压中的血管炎症。我们研究了正常血压的（布朗-挪威）大鼠、高血压的（达尔）大鼠和同源染色体 2 被从布朗-挪威大鼠转移到达尔大鼠的同系大鼠（SSBN2）。通过尾套测量的收缩压和通过定量 RT-PCR 测量的主动脉前内皮素 mRNA，在达尔大鼠中比布朗-挪威大鼠升高，在 SSBN2 大鼠中比达尔大鼠降低（P<0.01）。与布朗-挪威大鼠相比，达尔大鼠表现出炎症标志物和介质的增加，如核易位的 NF-kappaB 的主动脉 p65 亚单位以及 VCAM-1、ICAM-1、趋化因子（C-C 基序）受体 5 和 CD4 mRNA，所有这些都在 SSBN2 大鼠中降低。与布朗-挪威大鼠相比，主动脉 CD8 mRNA 在达尔和 SSBN2 大鼠中同样增加。与达尔大鼠相比，SSBN2 大鼠主动脉中的 CD4(+)T 细胞浸润减少，而 SSBN2 大鼠中与调节性 T 细胞谱系相关的三个标志物——Foxp3b 和免疫抑制剂转化生长因子（TGF）-β(1)和 IL-10 的主动脉蛋白表达增强。体外 T 细胞的激活表明，在 SSBN2 大鼠中，CD4(+)CD25(+)和 CD8(+)CD25(+)细胞（Tregs）产生 IL-10。因此，在遗传性盐敏感高血压啮齿动物模型中，血管炎症反应和高血压的增加通过将染色体 2 从正常血压的大鼠转移而减少，这与免疫抑制介质水平的增强有关。
