Laboratory of Pharmacology, Department of Drugs and Medicines, School of Pharmaceutical Sciences, São Paulo State University (UNESP), Rodovia Araraquara-Jau Km 01, Araraquara, São Paulo, 14800-903, Brazil.
Pflugers Arch. 2024 Mar;476(3):351-364. doi: 10.1007/s00424-024-02904-5. Epub 2024 Jan 17.
Despite the importance of physiological responses to stress in a short-term, chronically these adjustments may be harmful and lead to diseases, including cardiovascular diseases. The lateral hypothalamus (LH) has been reported to be involved in expression of physiological and behavioral responses to stress, but the local neurochemical mechanisms involved are not completely described. The corticotropin-releasing factor (CRF) neurotransmission is a prominent brain neurochemical system implicated in the physiological and behavioral changes induced by aversive threats. Furthermore, chronic exposure to aversive situations affects the CRF neurotransmission in brain regions involved in stress responses. Therefore, in this study, we evaluated the influence of CRF neurotransmission in the LH on changes in cardiovascular function and baroreflex activity induced by chronic variable stress (CVS). We identified that CVS enhanced baseline arterial pressure and impaired baroreflex function, which were followed by increased expression of CRF, but not CRF, receptor expression within the LH. Local microinjection of either CRF or CRF receptor antagonist within the LH inhibited the baroreflex impairment caused by CVS, but without affecting the mild hypertension. Taken together, the findings documented in this study suggest that LH CRF neurotransmission participates in the baroreflex impairment related to chronic stress exposure.
尽管生理应激反应在短期时间内很重要,但长期来看,这些调整可能是有害的,并导致疾病,包括心血管疾病。据报道,外侧下丘脑(LH)参与表达对压力的生理和行为反应,但涉及的局部神经化学机制尚不完全描述。促肾上腺皮质释放因子(CRF)神经传递是一个突出的脑神经化学系统,涉及到厌恶威胁引起的生理和行为变化。此外,慢性暴露于厌恶情境会影响参与应激反应的脑区域中的 CRF 神经传递。因此,在这项研究中,我们评估了 LH 中的 CRF 神经传递对慢性可变应激(CVS)引起的心血管功能和压力反射活动变化的影响。我们发现,CVS 增强了基础动脉压并损害了压力反射功能,随后 CRF 在 LH 内的表达增加,但 CRF 受体表达没有增加。在 LH 内局部微注射 CRF 或 CRF 受体拮抗剂抑制了 CVS 引起的压力反射功能障碍,但不影响轻度高血压。总之,本研究中的发现表明,LH CRF 神经传递参与了与慢性应激暴露相关的压力反射功能障碍。