High-salt intake is known to induce pathogenic T helper (Th) 17 cells and hypertension, but contrary to what is known, causes hypertension only in salt-sensitive (SS) individuals. Thus, we hypothesized that Th cell polarity determines salt sensitivity and hypertension development. Cultured splenic T cells from Dahl SS and salt-resistant (SR) rats subjected to hypertonic salt solutions were evaluated via ELISA, flow cytometry, immunocytochemistry and RT-qPCR. Seven-week-old SS and SR rats were fed a chow (CD) or high-salt diet (HSD) for 4 weeks, with weekly measurements of systolic blood pressure. The relaxation response of the aorta rings to the cumulative addition of acetylcholine was measured ex vivo. In these experimental animals, the Th cell polarity (Th17 and T regulatory [Treg]), the expression of Th17- or Treg-related genes, and the enrichment of the transcription factors RORγt and FOXP3 on the target gene promoter regions were determined via flow cytometry, RT-qPCR, and chromatin immunoprecipitation. Hypertonic salt solution induced Th17 and Treg cell differentiation in cultured splenic T cells isolated from SS and SR rats, respectively. HSD induced hypertension, endothelial dysfunction and proinflammatory Th17 cell differentiation only in SS rats. The enrichment of RORγt on the promoter regions of Il17a and Il23r increased their expression only in SS rats. Regardless of HSD, SR rats remained normotensive with Treg polarity, causing high Treg-related gene expressions (Il10, Cd25 and Foxp3). This study demonstrated that Th cell polarity determines salt sensitivity and drives hypertension development. SR rats were protected from HSD-associated hypertension via anti-inflammatory Treg polarity.

众所周知，高盐摄入会诱发致病性 T 辅助细胞 (Th) 17 细胞和高血压，但与已知的情况相反，高盐摄入仅在盐敏感 (SS) 个体中引起高血压。因此，我们假设 Th 细胞极性决定盐敏感性和高血压的发生。通过 ELISA、流式细胞术、免疫细胞化学和 RT-qPCR 对来自 Dahl SS 和耐盐 (SR) 大鼠的培养脾 T 细胞进行高渗盐溶液评估。七周大的 SS 和 SR 大鼠被喂食饲料 (CD) 或高盐饮食 (HSD) 4 周，每周测量收缩压。离体测量主动脉环对乙酰胆碱累积添加的松弛反应。在这些实验动物中，通过流式细胞仪测定了 Th 细胞极性（Th17 和 T 调节性 [Treg]）、Th17 或 Treg 相关基因的表达以及靶基因启动子区域转录因子 RORγt 和 FOXP3 的富集。细胞计数、RT-qPCR 和染色质免疫沉淀。高渗盐溶液分别诱导从 SS 和 SR 大鼠分离的培养脾 T 细胞中的 Th17 和 Treg 细胞分化。HSD 仅在 SS 大鼠中诱导高血压、内皮功能障碍和促炎 Th17 细胞分化。RORγt 在Il17a和Il23r启动子区域的富集仅在 SS 大鼠中增加了它们的表达。无论HSD如何，SR大鼠血压均保持正常，且Treg极性不变，导致Treg相关基因高表达（Il10、Cd25和Foxp3）。这项研究表明，Th 细胞极性决定盐敏感性并驱动高血压的发生。通过抗炎 Treg 极性，可以保护 SR 大鼠免受 HSD 相关高血压的影响。