International Journal of Molecular Medical Science, 2025, Vol.15, No.5, 235-243 http://medscipublisher.com/index.php/ijmms 237 3 Mechanism of Action and Theoretical Basis of ACEI/ARB Drugs 3.1 Inhibition of the renin-angiotensin-aldosterone system ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) mainly function by inhibiting the renin-angiotensin-aldosterone system (RAAS). RAAS is crucial in regulating blood pressure and renal blood flow. ACEI can prevent angiotensin I from converting into angiotensin II, while ARB can prevent angiotensin II from binding to the AT1 receptor. Both of these drugs can reduce vasoconstriction and sodium retention, prevent fibrosis caused by angiotensin II, and thereby lower blood pressure and glomerular pressure (Figure 1) (Alcocer et al., 2023). An overly active RAAS system can exacerbate kidney damage and proteinuria, which is particularly important for elderly patients with hypertension. Figure 1 Mechanism of action for angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEis) (Adopted from Alcocer et al., 2023) In addition to their blood pressure-lowering effects, ACEI and ARB also have some differences in drug properties. ACEI can increase blood potassium levels and promote the synthesis of nitric oxide (NO), thereby causing blood vessels to dilate. However, this mechanism may provide better protection for the kidneys and cardiovascular system to a certain extent (Alcocer et al., 2023). These differences can also illustrate their distinctions in actual therapeutic effects: Studies have found that ACEI usually performs better in slowing down the rate of renal function deterioration and reducing the risk of death in patients with chronic kidney disease (Zhang et al., 2020). 3.2 Improvement of renal blood flow and microcirculation ACEI and ARB improve blood flow and microcirculation in the kidneys by inhibiting RAAS activity and reducing glomerular pressure. This improvement can help maintain the glomerular filtration rate (GFR) and prevent renal function from deteriorating further, especially beneficial for elderly hypertensive patients with microvascular problems (Blazek and Bakris, 2023). At the same time, improving the blood supply to the kidneys can also reduce the risk of damage caused by ischemia and slow down the progression of chronic kidney disease. Studies have shown that even for patients with heart failure or severe hypertension, ARB may have a relatively significant effect in restoring renal blood flow and alleviating poor renal function (Kratky et al., 2021). These drugs can also enhance the efficacy of nitric oxide use, alleviate oxidative stress, thereby maintaining the health of renal microvessels and reducing the occurrence of renal hypoxia and fibrosis (Alcocer et al., 2023). Finally, these effects can help maintain the stability of kidney function and reduce urine protein - urine protein is a key indicator for determining whether the kidneys are protected. 3.3 Anti-inflammatory and anti-fibrotic effects ACEI and ARB also have obvious anti-inflammatory and anti-fibrotic effects. They can prevent the generation of pro-inflammatory factors, reduce the expression level of adhesion molecules, and lower the level of C-reactive
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