Spironolactone in heart failure
Spironolactone is a potassium-sparing diuretic that exerts its effect in the distal tubule. It is a specific antagonist of the mineralocorticoid receptor (MR). After binding the mineralocorticoid receptor, the complex changes its conformation and is not able to bind the mineralocorticoid receptor responsive element (MRE) on the DNA in the
nucleus. Spironolactone thus counteracts the actions of aldosterone and therefore has a natriuretic and potassium-sparing effect. Spironolactone also affects the aldosterone receptors in the heart. It is believed to reduce myocardial fibrosis and fibroblast proliferation, preventing further remodelling and dysfunction. It may improve survival in patients with severe heart failure. Spironolactone is used as maintenance therapy in severe heart failure, and other diuretics (such as furosemide) can be co-prescribed for the relief of symptoms of heart failure when indicated.
Which of the following effects does spironolactone have on the pathophysiology of heart failure?