How Little Aldosterone is Able to Raise Blood Pressure?

After its first description, primary aldosteronism was long felt to be a rare condition (1). More recently, a debate has been ongoing about the true prevalence of primary hyperaldosteronism (2). Primary aldosteronism is caused by bilateral adrenal hyperplasia, by aldosterone-producing adenoma, more rarely by primary adrenal hyperplasia, aldosterone-producing malignancies, or infrequent genetic syndromes (3). Since the early 1980s, ever higher proportions of hypertensive patients were diagnosed as having primary aldosteronism after the plasma aldosterone:renin ratio was introduced as a diagnostic tool and as an index of aldosterone synthesis out of proportion to the stimulation by the renin-angiotensin system (RAS) (4). This epidemiologic tsunami prompted the sarcastic question “Is there an unrecognized epidemic of primary aldosteronism?” (2). Because of the limited sensitivity and specificity of the aldosterone/renin ratio, because of problems collecting truly representative cohorts of hypertensive patients and further issues, past estimates of up to 40% of hypertensive patients having primary hyperaldosteronism are certainly exaggerated, although it remains certainly wise to screen patients with a higher a priori probability of primary hyperaldosteronism ( i.e. , patients with hypertension plus hypokalemia, young patients with hypertension, hypertension in a patient with an incidental adrenal mass, and patients with severe or resistant hypertension (3)). Nevertheless, there is increasing evidence that even in the absence of overt primary hyperaldosteronism more subtle faults in the regulation of aldosterone synthesis play a role in the genesis of so-called essential or primary hypertension. First, there is impressive evidence that for patients with resistant hypertension spironolactone is very effective for the control of blood pressure (BP) (5). One recent example is the efficacy of spironolactone as a fourth-line treatment in the ASCOT trial (6). Even more compelling is the Framingham offspring study in which Vasan found in nonhypertensive individuals a significant relationship between the serum aldosterone concentration …