What Are Aldosterone Antagonists?

Aldosterone has a variety of pathophysiological effects, can cause central hypertension, accelerate endothelial damage (enhanced by catecholamines), reduce heart rate variability, induce ventricular arrhythmias, promote sodium retention, potassium and magnesium loss, promote myocardial fibrosis and necrosis And inflammation, damage the fibrinolytic system. Non-selective aldosterone receptor antagonist spironolactone can reduce the mortality of patients with congestive heart failure, but male sex hyperplasia and other side effects related to sex hormones limit its application in the treatment of hypertension.

Aldosterone antagonist

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Aldosterone has a variety of pathophysiological effects, can cause central hypertension, and accelerate endothelial damage (

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Aldosterone antagonist diuresis

Because aldosterone can bind to aldosterone receptors located in the distal end of tubules and in the cytoplasm of collecting duct epithelial cells, aldosterone-receptor complexes are formed. This complex can be transferred into the nucleus, and has the role of inducing specific DNA transcription and translation, producing aldosterone-inducing proteins, activating Na ⁺ channels in the lumen membrane, and increasing its permeability. Na ⁺ is reabsorbed in the tubule fluid and increases the negative potential, thereby increasing the driving force for K ⁺ excretion and increasing K ⁺ excretion; while the chemical structure of aldosterone antagonists is similar to aldosterone, it can also bind to aldosterone receptors and compete Blocking the binding of aldosterone and receptors, antagonizing the regulation of Na ⁺ reabsorption and K ⁺ excretion by aldosterone, increasing Na ⁺ and water excretion, increasing urine output, reducing K ⁺ excretion, and acting as a potassium diuretic ^[1] .

Aldosterone antagonist hypertension

At present, hyperaldosteroneemia is a common cause of hypertension. Many research results have found that aldosterone antagonists are suitable for hypertension when diuretics, ACEI and ARB are not well combined.

Aldosterone antagonist heart failure

Aldosterone has independent and adverse effects on heart structure and function, such as causing endothelial dysfunction, vascular inflammation, and myocardial fibrosis. (Remodeling function of myocardium and vascular wall.) Short-term use of ACEI in the treatment of heart failure. Aldosterone declines. When patients with heart failure use ACEI for a long time, the once-decreased plasma aldosterone levels often rise again. In addition, other pathways such as low sodium or corticotropin can also increase aldosterone levels. Therefore, the addition of aldosterone receptor antagonists on the basis of ACEI can help further suppress the harmful effects of aldosterone. As mentioned above, in addition to the classical pathway, there are other alternatives to the production of AngII. Including cathepsin G, tissue plasminogen activator, elastase, and chymase have 20 times higher catalytic activity than ACE. It is not inhibited by ACEI and does not degrade bradykinin. Current research shows that aldosterone can promote cardiac muscle cell hypertrophy, fibroblast proliferation, and collagen production, leading to fibrosis of the heart muscle and surrounding blood vessels, blocking myocardial uptake of adrenaline, and increasing levels of plasminogen activator inhibitors. At the same time, it can cause vascular injury, endothelial dysfunction, and reduce vascular compliance. In addition to potassium retention and diuretic effects, aldosterone receptor antagonists can prevent fibrosis of the myocardium and surrounding blood vessels, but do not affect the repair of myocardial tissues and scar formation, improve diastolic and contractile functions, and improve cardiac remodeling. Can reduce plasma catecholamine levels and reduce ventricular ectopic agitation. At the same time, aldosterone receptor antagonists can also change heart rate variability and baroreflex sensitivity. These are beneficial for patients with heart failure ^[2] .

Atrial fibrillation

Several clinical experiments have shown that angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists can inhibit ventricular remodeling and reduce the incidence of atrial fibrillation. Studies have shown that aldosterone receptor antagonists can reduce mortality in patients with heart failure and left ventricular dysfunction after myocardial infarction.This study has shown that aldosterone receptor antagonists can reduce the incidence of atrial fibrillation in patients with hypertension and chronic heart failure. Thereby improving the prognosis, preventing complications and reducing the hospitalization rate. Therefore, spironolactone can be used as an indispensable therapeutic agent for patients with atrial fibrillation to prevent cardiac remodeling and improve prognosis.