Does ACE phenotype predict the acute antihypertensive response to ACE inhibition?

Inhibition of angio-converting enzyme (ACE) is one of the cornerstones of the
medical treatment of hypertension. Although ACE inhibitors on average are
effective antihypertensive agents, the blood pressure response to these agents
between subjects is highly variable. This variation in part depends on the
extent the renin-angiotensin system is activated, but supposedly also depends
to a large extent on (tissue) ACE activity. ACE activity shows a large
inter-individual variation, which only partly can be explained by the
frequently occurring polymorphysism (II, ID and DD) of the gene encoding for
ACE.

The aim of our study is to find out if and if so to what extent the acute blood
pressure lowering response to ACE-inhibition depends on the variation in the
ACE-phenotype. If the blood pressure response depends on ACE acitivity,
measurement of ACE-activity prior to starting antihypertensive therapy can be
used as a simple tool to select proper antihypertensive therapy, making
individualized antihypertensive therapy instead of the usual trial and error
approach possible.

The study is conducted as a single-blind, partly placebo-controlled, randomised
trial. At an interval of three weeks patients receive either a single acute
dose of an ACE-inhibitor (enalapril 20 mg) or a single placebo. Under
standardized conditions blood pressure is measured for 24-hours by means of an
ambulatory blood pressure monitor and blood for determination of ACE-activity,
ACE-concentration and other components of the renin-angiotensin system is
sampled at regular intervals. The blood pressure response to a single dose of
the ACE-inhibitor is also studied at a third study day after pretreatment with
a low dose of a thiazide diuretic (hydrochlorothiazide 12.5 mg once daily).
With this approach it can be found out if acitvation of the renin-angiotensin
system is a more important determinant of the acute blood pressure response to
an ACE-inhibitor than ACE-activity itself. Each study day is separated by a
rest period of three weeks. All participants are adviced about a normal salt
intake of 6 grams daily.

The interventions consist of administration of a single oral dose of an
ACE-inhibitor or placebo as well a administration of a single oral dose of an
ACE-inhibitor after pretreatment with a thiazide diuretic (hydrochlorothiazide
12.5 mg once daily) for one week.

The burden is only the time investment. Per patient three study days are
planned. During these days patients are at the research room for 6 hours.