Effect of a standard oral salt loading test on the renin-angiotensin-aldosterone system in healthy subjects - assessment of reference values

Recent data have shown primary aldosteronism (PA) to be the most frequent cause
of secondary hypertension, with reported prevalence rates of 5-12% among
hypertensive subjects in hypertension units as well as in primary care centers.
Diagnosing PA is clinically relevant, as causal treatment is feasible in case
of a aldosteron producing adrenal tumour - hypertension can be cured through an
adrenalectomy. in case of bilateral adrenal hyperplasia, targeted drug therapy
can be offered.
The diagnostic approach of PA contains 3 subsequent phases: screening
hypertensive subjects (plasma potassium, renin and aldosteron measurements),
confirmation tests (demonstrating increased plasma and/or aldosteron levels in
serum and/or urine after oral/intravenous salt loading, several test protocols)
and localisation studies (MRI/CT, adrenal venous sampling).
Screening for PA in hypertensive patients is usually done by measuring serum
aldosterone (increased in PA) and plasma renin (decreased in PA). The ratio of
these measurements - called the aldosterone- renin ratio - is currently the
most frequently used screening test to detect PA. Plasma renin can be assessed
by measurement of enzyme activity (plasma renin activity, PRA), in which the
generation of angiotensin-I is measured with a RIA. PRA measurements have some
disadvantages: chilled specimen collection, time consuming and relative large
intra- and interassay variation coefficients. Alternatively, plasma renin
concentration (PRC) can also be assessed. Advantages of the PRC compared to PRA
are: specimen collection at room temperature, possibility of automated analysis
and less intra- and interassay variation.
Until now, reference values for plasma renin in healthy and hypertensive
subjects have been based on PRA measurements. Although the influence of age on
plasma renin and aldosterone levels has been recognized long time ago, age
dependent reference values are presently not available.
Oral contraceptives (OC's) affect the renin-angiotensin-aldosterone system,
through stimulation of the hepatic angiotensinogen synthesis by the
ethinylestradiol component. OC's result in a slight increase of PRA (from more
endogenous substrate) and a decrease of plasma renin secretion (slight increase
of angiotensin-II inhibits renin secretion through negative feedback mechanism).
An alternative screening method for PA is to assess the urinary aldosterone
secretion. Aldosterone is secreted into urine as free-aldosterone and as
several metabolites ( mainly aldosterone18-glucuronide en
3alpha,5beta-tetrahydroaldosterone). It has been suggested that a normal
24-hour urinary aldosterone excretion excludes the presence of PA, but data are
limited.

- assessment of age dependent reference values (ages 20 - 70 yrs) for
plasma
renin (activity and concentration), serum aldosterone and 24h urinary
aldosterone (free and metabolites) during a regular diet and after a 3 day
oral
salt loading test

- validation of plasma renin concentration assay against PRA

- to evaluate the effect of OC's on plasma renin concentration and PRA
measurements

Diet intervention study.

All participants will be exposed to a standard oral salt loading test.

- 2 venapunctions (blood volume 1st venapunction: 21.5 ml, 2nd
venapunction
19.5 ml)
- 24 hour urine collection (2x)
- answering a few sreening questions:
a. medication
b. past medical history
- limited physical examination: blood pressure (2x), body weight, height