Lisinopril mech of action
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Summary
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These studies suggest lisinopril reduces blood pressure, protects the heart, aids in cardiomyocyte recovery, and has potential benefits in treating hypoxemic pulmonary hypertension and nephrotic syndrome, likely through its effects on the renin-angiotensin system and ACE2 modulation.
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Mechanism of Action of Lisinopril
Introduction to Lisinopril and ACE Inhibition
Lisinopril is a lysine analog of enalaprilat, the active metabolite of enalapril, and functions as an angiotensin-converting enzyme inhibitor (ACEI). Unlike enalapril, lisinopril is not a prodrug and exhibits equal efficacy and potency in ACE inhibition with a slightly longer duration of action after oral administration.
ACE Inhibition and Blood Pressure Regulation
Lisinopril works by inhibiting the angiotensin-converting enzyme (ACE), which is crucial in the renin-angiotensin-aldosterone system (RAAS). By blocking ACE, lisinopril reduces the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor. This leads to decreased vasoconstriction and reduced secretion of aldosterone, resulting in lower blood pressure . The inhibition of ACE also increases plasma renin activity due to the feedback mechanism.
Cardioprotective Effects
Lisinopril has demonstrated cardioprotective effects in various studies. It enhances the recovery of cardiomyocytes during reoxygenation and reduces oxidative damage, likely through mechanisms involving the endogenous renin-angiotensin system and direct cellular actions. Additionally, lisinopril has been shown to have a protective effect in experimental autoimmune myocarditis in rats, reducing inflammation and serum biomarkers associated with cardiac damage.
Interaction with Serum Proteins
Lisinopril binds to bovine serum albumin (BSA) under physiological conditions, forming a complex that slightly alters the conformation of BSA while retaining its α-helical structure. The binding is spontaneous and primarily involves van der Waals forces and hydrogen bonding. This interaction may influence the pharmacokinetics and distribution of lisinopril in the body.
Effects on Pulmonary Vasoconstriction
Lisinopril has been found to attenuate acute hypoxic pulmonary vasoconstriction in humans. This suggests that angiotensin II plays a modulatory role during hypoxic pulmonary vasoconstriction, and ACE inhibition can be beneficial in managing hypoxemic pulmonary hypertension.
Influence on ACE2 Levels
Recent studies have shown that oral lisinopril increases tissue levels of ACE2, the receptor for SARS-CoV-2, in various tissues including the small intestine, lung, kidney, and brain. This increase in ACE2 levels could have implications for the transmission and pathogenesis of COVID-19.
Conclusion
Lisinopril is a potent ACE inhibitor that effectively reduces blood pressure by inhibiting the conversion of angiotensin I to angiotensin II. It offers cardioprotective benefits, reduces oxidative damage, and has potential implications in pulmonary hypertension and COVID-19 due to its effect on ACE2 levels. Understanding these mechanisms helps in optimizing its use in clinical settings for managing hypertension and related cardiovascular conditions.
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