Ramipril mechanism of action
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Ramipril Mechanism of Action: Angiotensin-Converting Enzyme (ACE) Inhibition
Ramipril is an angiotensin-converting enzyme (ACE) inhibitor. Its main mechanism is to block the conversion of angiotensin I to angiotensin II, a powerful vasoconstrictor. By reducing angiotensin II levels, ramipril leads to vasodilation, which lowers blood pressure. Additionally, this inhibition decreases aldosterone secretion, promoting diuresis and natriuresis, and increases bradykinin levels, which further supports vasodilation and may contribute to some of its beneficial effects .
Effects on the Renin-Angiotensin System and Blood Pressure
By inhibiting ACE, ramipril reduces the formation of angiotensin II, resulting in lower blood pressure and less strain on the heart. This effect is central to its use in treating hypertension and heart failure 16. In animal studies, ramipril at antihypertensive doses prevented increases in blood pressure and left ventricular hypertrophy, while lower doses that did not affect blood pressure still showed some protective effects on the heart 3810.
Bradykinin Potentiation and Cardiovascular Protection
ACE is also responsible for breaking down bradykinin, a peptide that promotes vasodilation. By inhibiting ACE, ramipril increases bradykinin levels, which can enhance its antihypertensive and antihypertrophic effects. Studies show that blocking bradykinin receptors can abolish some of ramipril’s protective effects on the heart, indicating that bradykinin plays a significant role in these benefits 810. However, some research suggests that certain antiatherosclerotic effects of ramipril are independent of bradykinin potentiation .
Anti-Inflammatory and Antioxidant Actions
Ramipril also exhibits anti-inflammatory and antioxidant properties. It reduces the expression of adhesion molecules like ICAM-1 and VCAM-1 in endothelial cells, especially under high-glucose conditions, by inhibiting the MAPK/ERK signaling pathway. This action may help prevent atherosclerosis . Additionally, ramipril increases the resistance of LDL to oxidation, further contributing to its antiatherosclerotic effects .
Antifibrotic and Antihypertrophic Effects
Ramipril helps prevent and reduce cardiac fibrosis and left ventricular hypertrophy. It does this by downregulating factors like activin A and collagen in the heart, which are associated with tissue remodeling after injury or in chronic hypertension 410. These effects are partly independent of blood pressure reduction and may involve both angiotensin II inhibition and bradykinin potentiation 810.
Additional Protective Mechanisms
Ramipril has been shown to restore the expression of protective cardiac receptors (PPARβ/δ and PPARγ) and reduce oxidative stress in models of heart failure and cardiomyopathy, although its ability to restore full cardiac function may be limited in severe cases . It also demonstrates neuroprotective effects in models of peripheral neuropathy, with evidence pointing to the involvement of the angiotensin II type 2 receptor (AT2) in these benefits .
Conclusion
Ramipril’s primary mechanism of action is the inhibition of ACE, leading to reduced angiotensin II and increased bradykinin levels. This results in vasodilation, lower blood pressure, and reduced cardiac workload. Beyond these effects, ramipril also provides anti-inflammatory, antioxidant, antifibrotic, and neuroprotective benefits through multiple pathways, including modulation of signaling molecules and receptors. These combined actions make ramipril a valuable medication for cardiovascular and related conditions 12346789+1 MORE.
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