International Journal of Molecular Medical Science, 2025, Vol.15, No.5, 235-243 http://medscipublisher.com/index.php/ijmms 236 2 The Pathophysiological Mechanism of Renal Damage Caused by Hypertension 2.1 Hemodynamic changes Long-term hypertension can cause blood pressure throughout the body and within the kidneys to remain at a persistently high level, thereby leading to changes in the structure and function of the kidney's blood vessels. Elevated blood pressure affects the input small arteries and glomerulus, increasing the transparency of the blood vessel walls, making them stiff and narrowing the lumen. These changes can interfere with the normal blood flow and filtration function of the kidneys. Continuous blood flow pressure may cause insufficient glomerular blood supply and hypoxia, creating conditions for subsequent renal injury and the occurrence of proteinuria (Gaydarski et al., 2024). With the progression of the disease, the above changes may further cause glomerular sclerosis and tubulointerstitial fibrosis, which is regarded as the main pathological feature of hypertensive nephropathy (Costantino et al., 2021). In patients with hypertension, the renin-angiotensin-aldosterone system (RAAS) is often overactive, thereby exacerbating the damage to the kidneys in terms of blood flow. Angiotensin II is a key active factor in RAAS. It causes vasoconstriction, increases the pressure of glomerular capillaries, and promotes the retention of sodium salts in the body, further exacerbating hypertension and renal function impairment. In addition, enhanced renal sympathetic nerve activity and vascular structure remodeling can also cause abnormal renal blood flow, resulting in an unbreakable vicious cycle between renal injury and hypertension (Hao et al., 2024; Kim, 2024). 2.2 Endothelial dysfunction Endothelial dysfunction is one of the important characteristics of hypertension-related renal damage, mainly manifested as a decrease in the production of nitric oxide (NO), an increase in oxidative stress, and a more intense response to vasoconstrictor factors such as angiotensin II and endothelin-1. These changes will reduce the ability of blood vessels to dilate, deteriorate vascular elasticity, and also promote the adhesion of white blood cells to blood vessels and increase vascular permeability, thereby causing renal microvascular injury (Gaydarski et al., 2024). When in a state of hypertension, the number of endothelial microparticles in the blood increases and the function of endothelial progenitor cells is impaired. This is an early signal of abnormal endothelial function and will further aggravate renal lesions (Zhang et al., 2025). The main causes of such functional problems include the activation of inflammatory signals (such as the NF-κB pathway), increased oxidative stress responses, and damage to cortical structure. These changes can affect the normal operation of the glomerular filtration barrier, cause proteinuria, and accelerate the deterioration of renal function. ACE inhibitors and ARB drugs can improve vascular endothelial function by enhancing the effect of nitric oxide and reducing oxidative stress responses. Maintaining stable vascular endothelial function can prevent renal injury caused by hypertension (Wang and He, 2024). 2.3 Inflammatory and fibrotic responses Kidney damage caused by hypertension is closely related to the long-term inflammatory and fibrotic processes. Persistent hypertension promotes the activation of immune cells such as T cells and macrophages and their entry into the kidneys, releasing inflammatory factors such as IL-6, IL-17, and TNF-α, thereby intensifying tissue damage, attracting more white blood cells to enter the kidneys, and affecting their normal structure (Lin et al., 2022; Hao et al., 2024). Meanwhile, inflammatory signaling pathways such as NF-κB remain active continuously, further intensifying the inflammatory response and causing long-term kidney damage. Fibrosis often occurs when inflammation and blood flow damage develop to a certain extent. Factors that promote fibrosis (such as angiotensin II) can cause excessive production of extracellular matrix proteins, leading to hardening of the glomerulus and fibrosis of the tissues around the renal tubules. Among them, epithelial-mesenchymal transition (EMT) and the activation of fibroblasts are the key processes leading to irreversible scar formation and continuous deterioration of renal function (Costantino et al., 2021). Therefore, therapeutic approaches targeting inflammation and fibrosis-related pathways, such as the use of RAAS inhibitors or anti-inflammatory drugs, play an important role in reducing renal injury related to hypertension and protecting renal function (Guzik et al., 2024).
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