Lisinopril action mechanism
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Mechanism of Action of Lisinopril
Angiotensin-Converting Enzyme (ACE) Inhibition
Lisinopril is a potent angiotensin-converting enzyme (ACE) inhibitor that works by blocking the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor. This inhibition leads to vasodilation, reduced blood pressure, and decreased aldosterone secretion, which increases sodium and water excretion. By reducing angiotensin II levels, lisinopril also diminishes its effects on the cardiovascular system, including vasoconstriction and aldosterone-mediated sodium retention.
Cardioprotective Effects
Oxidative Stress and Cardiomyocyte Protection
Lisinopril has been shown to enhance the recovery of cardiomyocytes during reoxygenation and reduce oxidative damage. It significantly improves the viability of cardiomyocytes exposed to oxidative agents like ammonium persulfate and tertbutylhydroperoxide, suggesting a protective role against oxidative stress. Additionally, lisinopril upregulates antioxidant proteins such as catalase, SOD2, and thioredoxin in human cardiomyocytes, further protecting against oxidative stress and fibrosis.
Pulmonary Vasoconstriction
Lisinopril also attenuates acute hypoxic pulmonary vasoconstriction (HPV) in humans. It significantly blunts the increase in mean pulmonary artery pressure and total pulmonary vascular resistance induced by hypoxemia, indicating that angiotensin II plays a modulatory role during HPV.
Renal Protection
Chronic Glomerulonephritis
In cases of chronic glomerulonephritis, lisinopril exerts a potent antiproteinuric effect and suppresses the progression of glomerulosclerosis and tubulointerstitial fibrosis. It helps recover the reduced number of anionic charge sites on the glomerular basement membrane (GBM), thereby protecting against massive proteinuria. Lisinopril also reduces the expression of transforming growth factor-β (TGF-β) and plasminogen activator inhibitor-1 (PAI-1), improving extracellular matrix metabolism and preventing renal tissue damage.
Hematopoietic Stem Cell Protection
Lisinopril has been found to prevent the entry of murine hematopoietic stem cells into the cell cycle after irradiation. This effect is mediated through the increase of the hemoregulatory peptide AcSDKP, which inhibits the cycling of hematopoietic stem cells, thereby offering protection to the hematopoietic system.
Intestinal Absorption
Lisinopril is absorbed in the intestines via a nonpassive, peptide carrier-mediated transport system. Its absorption is relatively low compared to other ACE inhibitors, which explains its prolonged ACE inhibition and low oral bioavailability.
Conclusion
Lisinopril's mechanism of action primarily involves the inhibition of ACE, leading to reduced levels of angiotensin II and subsequent vasodilation. It offers cardioprotective effects by reducing oxidative stress and protecting cardiomyocytes, attenuates hypoxic pulmonary vasoconstriction, and provides renal protection in chronic glomerulonephritis. Additionally, it protects hematopoietic stem cells from irradiation-induced damage and is absorbed in the intestines through a carrier-mediated transport system. These multifaceted actions make lisinopril a valuable therapeutic agent in managing hypertension and related cardiovascular and renal conditions.
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