Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center of Translational Medicine for Cardiovascular Disease, Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu 211166, P.R. China.
Research Center for Cardiovascular and Cerebrovascular Diseases, The University of Duisburg‑Essen, Duisburg‑Essen University, D-45122 Essen, Germany.
Int J Mol Med. 2021 Jun;47(6). doi: 10.3892/ijmm.2021.4928. Epub 2021 Apr 13.
Present in more than one billion adults, hypertension is the most significant modifiable risk factor for mortality resulting from cardiovascular disease. Although its pathogenesis is not yet fully understood, the disruption of the renin‑angiotensin system (RAS), consisting of the systemic and brain RAS, has been recognized as one of the primary reasons for several types of hypertension. Therefore, acquiring sound knowledge of the basic science of RAS and the underlying mechanisms of the signaling pathways associated with RAS may facilitate the discovery of novel therapeutic targets with which to promote the management of patients with cardiovascular and kidney disease. In total, 4 types of angiotensin II receptors have been identified (AT1R‑AT4R), of which AT1R plays the most important role in vasoconstriction and has been most extensively studied. It has been found in several regions of the brain, and its distribution is highly associated with that of angiotensin‑like immunoreactivity in nerve terminals. The effect of AT1R involves the activation of multiple media and signaling pathways, among which the most important signaling pathways are considered to be AT1R/JAK/STAT and Ras/Raf/MAPK pathways. In addition, the regulation of the nuclear factor κ‑light‑chain‑enhancer of activated B cells (NF‑κB) and cyclic AMP response element‑binding (CREB) pathways is also closely related to the effect of ATR1. Their mechanisms of action are related to pro‑inflammatory and sympathetic excitatory effects. Central AT1R is involved in almost all types of hypertension, including spontaneous hypertension, salt‑sensitive hypertension, obesity‑induced hypertension, renovascular hypertension, diabetic hypertension, L‑NAME‑induced hypertension, stress‑induced hypertension, angiotensin II‑induced hypertension and aldosterone‑induced hypertension. There are 2 types of central AT1R blockade, acute blockade and chronic blockade. The latter can be achieved by chemical blockade or genetic engineering. The present review article aimed to highlight the prevalence, functions, interactions and modulation means of central AT‑1R in an effort to assist in the treatment of several pathological conditions. The identification of angiotensin‑derived peptides and the development of AT‑2R agonists may provide a wider perspective on RAS, as well as novel therapeutic strategies.
在超过 10 亿成年人中，高血压是心血管疾病导致死亡的最重要的可改变风险因素。尽管其发病机制尚未完全阐明，但肾素-血管紧张素系统（RAS）的破坏，包括系统性和脑 RAS，已被认为是几种类型高血压的主要原因之一。因此，获得有关 RAS 的基础科学和与 RAS 相关的信号通路的基本机制的知识，可能有助于发现新的治疗靶点，以促进心血管和肾脏疾病患者的管理。总共已经确定了 4 种血管紧张素 II 受体（AT1R-AT4R），其中 AT1R 在血管收缩中起着最重要的作用，并且研究得最为广泛。它在大脑的几个区域中被发现，其分布与神经末梢中血管紧张素样免疫反应性的分布高度相关。AT1R 的作用涉及到多种介质和信号通路的激活，其中最重要的信号通路被认为是 AT1R/JAK/STAT 和 Ras/Raf/MAPK 通路。此外，核因子 κ-轻链增强子激活的 B 细胞（NF-κB）和环磷酸腺苷反应元件结合（CREB）通路的调节也与 ATR1 的作用密切相关。它们的作用机制与促炎和交感兴奋作用有关。中枢 AT1R 参与几乎所有类型的高血压，包括自发性高血压、盐敏感性高血压、肥胖诱导的高血压、肾血管性高血压、糖尿病高血压、L-NAME 诱导的高血压、应激诱导的高血压、血管紧张素 II 诱导的高血压和醛固酮诱导的高血压。中枢 AT1R 阻断有 2 种类型，即急性阻断和慢性阻断。后者可以通过化学阻断或基因工程来实现。本文综述旨在强调中枢 AT1R 的普遍性、功能、相互作用和调节手段，以协助治疗几种病理状况。血管紧张素衍生肽的鉴定和 AT-2R 激动剂的开发可能为 RAS 提供更广泛的视角，并为新的治疗策略提供新的视角。
