Angiotensin II Tablet

After high concentrations of Ang II bind to the AT1 receptor, the NF - κ B pathway is activated by Gq PKC: I κ B kinase (IKK) activation → I κ B phosphorylation degradation → NF - κ B nuclear translocation → binding to inflammatory gene promoters, inducing the expression of inflammatory factors such as TNF - α, IL-6, IL-1 β, MCP-1, ICAM-1, VCAM-1, and adhesion molecules.
At the same time, Ang II activates the MAPK pathway (ERK1/2, JNK, p38MAPK): through the Gq Ras Raf cascade reaction, it promotes c-Fos and c-Jun nuclear translocation, forms AP-1 transcription factor, and synergistically amplifies inflammatory factor expression with NF - κ B.

Angiotensin II Tablet induced expression of adhesion molecules (ICAM-1, VCAM-1) promotes monocyte adhesion to vascular endothelium, transendothelial migration, and differentiation into macrophages in damaged tissues.
Ang II directly activates macrophages through AT1 receptors: promoting macrophage polarization towards M1 type (pro-inflammatory phenotype), releasing TNF - α, IL-6, ROS, and matrix metalloproteinases (MMPs), further damaging tissues and activating fibroblasts.

Vascular endothelial cells highly express AT1 receptors, and Ang II activation damages endothelial cells through the ROS pathway: reducing NO production, increasing endothelial permeability, disrupting endothelial barrier function, leading to plasma protein leakage, inflammatory cell infiltration, and the formation of a pro-inflammatory microenvironment.
After endothelial injury, vascular wall exposure, platelet activation and coagulation system activation further amplify inflammatory reaction and accelerate atherosclerosis and vascular fibrosis.

High concentration (10 ⁻⁸~10 ⁻⁶ mol/L): The affinity of AT1 receptor (KD=1-5 nM) is much higher than that of AT2 receptor (KD=50-100 nM), which preferentially activates AT1 pathological signals and drives pro-inflammatory and fibrotic damage;
Low concentration (10 ⁻¹²~10 ⁻¹⁰ mol/L): AT2 receptor binding is dominant, while promoting ACE2 expression, increasing Ang 1-7 production, activating AT2/Mas repair signaling, and exerting tissue repair regulatory effects;
Concentration threshold: 10 ⁻¹¹ mol/L is the critical concentration for functional transformation, above which concentration tends to cause pathological damage, and below which concentration tends to repair and regulate.

The damaged microenvironment can dynamically regulate the expression ratios of AT1, AT2, and Mas receptors, determining the function of Ang II
Pathological status (early injury/chronic inflammation): high expression of AT1 receptor, low expression of AT2/Mas receptor, Ang II preferentially activates AT1, driving inflammatory fibrosis damage;
Repair status (late stage of injury/regeneration stage): AT2/Mas receptor expression is significantly upregulated (5-10 times), AT1 receptor expression is downregulated, Ang II preferentially activates AT2/Mas, initiating repair signals;
Regulatory mechanism: Inflammatory factors (TNF - α, IL-6) upregulate AT1 receptors and inhibit AT2 receptors; Repair factors (IL-10, VEGF, Ang 1-7) upregulate AT2/Mas receptors and inhibit AT1 receptors.

The complex regulatory network formed by damaging the local microenvironment (inflammatory factors, growth factors, ECM components, oxygen partial pressure) determines the expression and signal bias of Ang II receptors
Inflammatory microenvironment (high TNF - α, IL-1 β, low oxygen): upregulates AT1, inhibits AT2/Mas, promotes pathological signal activation, and aggravates injury;
Repairing microenvironment (high IL-10, VEGF, Ang 1-7, normoxic): Upregulation of AT2/Mas, inhibition of AT1, promotion of repair signal activation, and acceleration of tissue regeneration;
ECM component: Collagen I (fibrotic type) upregulates AT1 receptor; Collagen III and fibronectin (repair type) upregulate AT2 receptors, forming positive feedback on ECM receptor expression.

Ang II receptors, especially GPCRs, exhibit signal bias: the same receptor can activate different downstream signaling pathways, depending on ligand concentration, receptor conformation, and microenvironment.
AT1 receptor bias: High concentration Ang II activates Gq/MAPK/NF - κ B (pathological bias); Low concentrations of Ang II can activate β - arrestin (protective bias), inhibit inflammation, and resist apoptosis;
AT2 receptor bias: Under repair microenvironment, AT2 receptor activation Gi2/3-PTP/Hippo inhibition (repair bias); Under pathological microenvironment, AT2 receptors can activate a small amount of MAPK (weak pathological bias).