Endocrine Abstracts

Aldosterone has important effects on blood pressure regulation and electrolyte haemostasis: recent data from Framingham confirm that plasma levels of the hormone predict subsequent development of hypertension in young adults, while our own data show that plasma aldosterone correlates with blood pressure in older subjects, and is inversely associated with birth weight. It is clear, therefore, that long-term regulation of aldosterone is important in setting blood pressure levels and determining cardiovascular dysfunction.

We have previously shown that levels of aldosterone in urine and plasma are heritable, and associated with common variants in the gene encoding aldosterone synthase. More recently, we reported that this was more closely linked to variation in the adjacent gene (CYP11B1) encoding 11βhydroxylase. This also is associated with loss of efficiency of conversion of deoxycortisol to cortisol. As a consequence, we also propose that there is a digenic effect that tends to increase aldosterone production, with inefficient 11βhydroxylation causing a long-term increase in ACTH drive to the adrenal, with enhanced expression of CYP11B2 (encoding aldosterone synthase) resulting in chronically raised aldosterone secretion in response to factors such as angiotensin 11 and potassium.

In susceptible subjects this is likely, over many years, to result in hypertension with relative aldosterone excess. The hypothesis is supported by very recent data in large population case–control studies of hypertension that show an association between the above variants and high blood pressure.