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These studies suggest ACE inhibitors are compounds used to treat hypertension, cardiovascular and renal diseases, and potentially diabetes-related complications, with ongoing research aimed at improving their efficacy and reducing side effects.
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Angiotensin-converting enzyme (ACE) inhibitors are a class of medications primarily used to treat hypertension (high blood pressure) and various cardiovascular and renal diseases. They work by inhibiting the activity of the enzyme ACE, which plays a crucial role in the renin-angiotensin system (RAS) that regulates blood pressure and fluid balance .
ACE inhibitors function by blocking the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor that increases blood pressure. By reducing the levels of angiotensin II, ACE inhibitors promote vasodilation (widening of blood vessels), decrease blood volume, and lower blood pressure . Additionally, they increase the levels of bradykinin, a vasodilatory peptide, which further helps in reducing blood pressure and improving cardiovascular health .
ACE inhibitors are highly effective in managing hypertension and have been shown to reduce mortality in patients with congestive heart failure and left ventricular dysfunction post-myocardial infarction. They also delay the progression of diabetic nephropathy and neuropathy, making them a critical component in the treatment of diabetes-related complications . Furthermore, ACE inhibitors have antioxidant properties that help stabilize plaques and prevent ischemic events, thereby offering protection against cardiovascular diseases .
Given the side effects associated with synthetic ACE inhibitors, such as hypotension, renal insufficiency, and hyperkalemia, there is a growing interest in natural ACE inhibitors derived from plants. Research has identified over 50 plant species with ACE-inhibitory activity, including Angelica keiskei, Momordica charantia, and Prunus domestica. These natural inhibitors often have lower toxicity and minimal side effects, making them promising candidates for developing safer antihypertensive drugs.
Recent studies have revealed that ACE consists of two domains (N- and C-domains) with different functions. This discovery has led to the development of domain-selective ACE inhibitors, which aim to reduce side effects and improve efficacy by targeting specific domains of the enzyme . Structural studies using X-ray crystallography have provided detailed insights into the active site of ACE, facilitating the rational design of next-generation inhibitors.
Compounds like N-(1-Deoxy-d-fructos-1-yl)-histidine (Fru-His), found in processed foods, have shown significant ACE inhibitory activity. These food-derived inhibitors are stable during digestion and interact effectively with the ACE active site, suggesting their potential use in functional foods to manage hypertension.
ACE inhibitors are a cornerstone in the treatment of hypertension and related cardiovascular and renal diseases. While synthetic ACE inhibitors are effective, their side effects have spurred interest in natural and domain-selective alternatives. Ongoing research continues to enhance our understanding of ACE inhibition, paving the way for safer and more effective treatments.
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