Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2012) 28 S11.4

SFEBES2012 Symposia Novel lessons form mineralocorticoid excess (4 abstracts)

New approaches to inhibition of mineralocorticoid action

John Connell

Department of Medicine, University of Dundee, Dundee, United Kingdom.

Aldosterone has assumed increasing importance as a major cardiovascular risk factor. This is illustrated by the positive correlation between plasma aldosterone levels and blood pressure in a number of large population surveys, and the finding that approximately 10% of patients with high blood pressure have inappropriate aldosterone levels in relation to renin, consistent with primary aldosteronism. Evidence also supports the notion that aldosterone exerts particularly deleterious effects on a range of target tissues including the heart, blood vessels and kidney. Thus, patients with primary aldosteronism have a significantly increased risk of stroke, myocardial infarction or cardiac rhythm problems while data from our own group have shown evidence of significant cardiac damage in patients with no previous history of myocardial disease. These findings indicate the importance of aldosterone as a target for cardiovascular therapy. Traditionally, mineralocorticoid receptor antagonists have been shown to be effective in the treatment of heart failure, and in reducing morbidity and mortality following myocardial infarction. However, these agents have limited value because of side effects and alternative approaches to reducing the effects of aldosterone are indicated. One opportunity is presented by the ability to inhibit the synthesis of aldosterone using small molecules that inhibit the conversion of early precursors to aldosterone within the adrenal cortex. The value of such an approach has recently been demonstrated clinically, showing that this approach could block aldosterone production and lower blood pressure. However, the value of this approach was limited by the fact that the agent used also had an effect on the production of cortisol. In summary, aldosterone is an important cardiovascular risk factor which requires targeted intervention. Approaches include antagonism of the mineralocorticoid receptor, and inhibition of aldosterone secretion. Further refinements in selective receptor blockade and in more specific inhibition of aldosterone synthesis are likely to be efficacious in the future.

Declaration of interest: There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Funding: No specific grant from any funding agency in the public, commercial or not-for-profit sector.

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