Stress is associated with an increased risk of hypertension, and the incidence of stress-related hypertension has risen rapidly in recent years; however, the underlying mechanisms remain elusive. Gut dysbiosis has been demonstrated to contribute to hypertension and hyperactivation of the hypothalamus-pituitary-adrenal (HPA) axis. Based on our previous findings showing the altered gut microbiota in the rats of stress-induced hypertension (SIH), the present study aims to investigate whether the stress-induced alteration in gut microbiota can lead to the dysfunction of the HPA axis which contributes to the development of SIH. SIH was developed in rats subjected to electric foot-shock combined with buzzer noise stressors. The gut microbiota of rats were deleted by administering an antibiotic cocktail containing ampicillin (1 g/L), vancomycin (500 mg/L), neomycin (1 g/L), and metronidazole (1 g/L) in drinking water. The serum levels of adrenocorticotropic hormone (ACTH) and corticosterone (CORT) were tested using enzyme-linked immunosorbent assay (ELISA). The mRNA expression of glucocorticoid receptor (GR) and corticotropin-releasing factor (CRF), CRFR1 and CRFR2 was detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The cellular protein expressions of corticotropin-releasing hormone (CRH), c-fos, and GR were examined by immunohistochemical staining. In the present study, SIH rats showed a hyperactive HPA axis as indicated by the increased CRH expression in the paraventricular nucleus (PVN) of the hypothalamus, the elevated serum ACTH or CORT concentrations, and increased adrenal gland index. The decreased GR expression and increased CRFR1 in the hypothalamus might underlie the hyperactivation of the HPA axis. The microbial deletion by antibiotics mitigated the hyperactivation of the HPA axis and attenuated the stress-induced elevation of blood pressure, indicating that the causal link of gut microbiota to SIH is mediated, at least in part, by the HPA axis activity. Our findings shed new light on the mechanisms underlying SIH.

压力与高血压风险增加有关，近年来压力相关高血压的发病率迅速上升；然而，潜在的机制仍然难以捉摸。肠道菌群失调已被证明会导致高血压和下丘脑-垂体-肾上腺 (HPA) 轴的过度激活。基于我们之前的研究结果显示，应激性高血压（SIH）大鼠肠道菌群发生了改变，本研究旨在探讨应激性高血压（SIH）大鼠肠道菌群的改变是否会导致 HPA 轴功能障碍，从而导致SIH 的发展。SIH 是在受到电足电击与蜂鸣器噪声压力源相结合的大鼠中产生的。通过给予含有氨苄青霉素 (1 g/L) 的抗生素混合物去除大鼠的肠道微生物群，饮用水中的万古霉素 (500 mg/L)、新霉素 (1 g/L) 和甲硝唑 (1 g/L)。使用酶联免疫吸附试验 (ELISA) 测试促肾上腺皮质激素 (ACTH) 和皮质酮 (CORT) 的血清水平。通过定量逆转录聚合酶链反应（qRT-PCR）检测糖皮质激素受体（GR）和促肾上腺皮质激素释放因子（CRF）、CRFR1和CRFR2的mRNA表达。通过免疫组织化学染色检查促肾上腺皮质激素释放激素 (CRH)、c-fos 和 GR 的细胞蛋白表达。在本研究中，SIH 大鼠表现出过度活跃的 HPA 轴，如下丘脑室旁核 (PVN) 中 CRH 表达增加、血清 ACTH 或 CORT 浓度升高以及肾上腺指数增加所示。下丘脑中 GR 表达的降低和 CRFR1 的增加可能是 HPA 轴过度激活的基础。抗生素导致的微生物缺失减轻了 HPA 轴的过度活化并减弱了压力引起的血压升高，表明肠道微生物群与 SIH 的因果关系至少部分是由 HPA 轴活动介导的。我们的研究结果揭示了 SIH 的潜在机制。