Hypertension is one of the most common medical problems in the
world today. Renovascular factors are a major cause of potentially
curable hypertension. Better noninvasive screening procedures for
identification of renovascular hypertensive patients are needed.
This article reviews the pathophysiology of renal artery stenosis,
the effects and pharmacology of angiotensin-converting enzyme (ACE)
inhibitors, the use of enalaprilat (Vasotec) in conjunction with
renal scintigraphy, and the patient selection criteria. Vasotec is
an effective, practical, and safe ACE inhibitor used to augment the
renogram study in screening patients for suspected renovascular
hypertension. For ACE inhibitor renograms to be cost-effective in
screening patients for suspected renovascular hypertension, strict
adherence to the guidelines of patient selection must be imposed by
referring physicians to ensure a prevalence rate of greater than
30% in the screened
Hypertension is one of the most common medical problems in the
world today. It affects nearly 60 million people in the United
States alone.1 Hypertensive cardiovascular disease is one of the
leading causes of death in the United States. Renovascular factors
remain a major cause of potentially curable hypertension, but
renovascular hypertension only may affect less than 1% of the
general population.2 With the advances in percutaneous transluminal
renal angioplasty (PTRA) and other surgical techniques, there is
profound interest in developing better noninvasive screening
procedures for the identification of patients with potentially
correctable causes of hypertension.3,4
Angiotensin-converting enzyme (ACE) inhibition used in
conjunction with renal radionuclide studies have been cited as a
good noninvasive study for the detection of significant renal
artery stenosis.5-12 Captopril (Capoten®) has been the traditional
ACE inhibitor used in the various study groups
published.10,11,13-16 There have been very few, if any, other ACE
inhibitors studied in conjunction with renal scintigraphy. The
observed sensitivity and specificity of several prospective studies
using captopril average 75% to 95% and 80% to 93%,
respectively.5,10,11,14,17-21 There are no published data using
other ACE inhibitors.
This article reviews the alterations in renal physiology in
patients with renal artery stenosis (RAS), the effects of ACE
inhibition, and the use of enalaprilat (Vasotec®) in conjunction
with renal scintigraphy in the evaluation of patients with possible
renal artery stenosis, as well as patient selection criteria.
Pathophysiology of renal artery stenosis and the effects ofACE
Constriction of the renal artery leads to a cascade of important
hemodynamic and humoral responses within the affected kidney.
Initially, there is an attempt to maintain blood flow by
vasodilatation distal to the stenotic site. With significant
stenosis, there is a decrease in distal renal artery pressure and
blood flow, leading to decreased renal perfusion pressure. When
this occurs, renin is released by the juxtaglomerular apparatus and
augments intrarenal angiotensin II production.
Within the affected kidney, the angiotensin II-dependent renal
vasoconstriction attenuates the fall in renal blood flow and
affects the glomerular filtration rate (GFR) by controlling the
vascular tone of the efferent renal arterioles. Angiotensin II
preferentially causes vasoconstriction of the efferent arterioles
to maintain transcapillary pressures within the glomerulus that
maintains the GFR of the affected kidney.22-27
However, in the presence of ACE inhibition, which blocks the
formation of angiotensin II, there would be a significant reduction
in the postglomerular efferent resistance and a decrease in the GFR
of the stenotic kidney. This decrease in individual renal
is assessed accurately and noninvasively using conventional
renal radionuclide studies.11,28
Other systemic effects of angiotensin II include the stimulation
of secretion and synthesis of aldosterone, antidiuretic hormone
(ADH), adrenocorticotropin (ACTH), epinephrine, and norepinephrine.
It causes generalized vasopressor effect on the smooth muscle cells
of the arterioles throughout the cardiovascular system, leading to
the elevation of systemic mean arterial pressure. These effects
likewise are suppressed by ACE inhibitors.
Pharmacology of ACE inhibitors
As noted above, a reduction in renal perfusion pressure results
in preferential angiotensin II mediated vasoconstriction of the
efferent arterioles in an attempt to maintain the GFR of the
stenotic kidney. ACE inhibitors block the formation of angiotensin
II, thereby interfering with the renin-angiotensin-aldosterone
system. This reduces the postglomerular efferent resistance,
decreasing the GFR of the stenotic kidney, renal blood flow, and
systemic blood pressure. It also inhibits the degradation of
bradykinin. Captopril (Capoten) is one of the widely used oral ACE
inhibitors on the market today. It also has been used and studied
in conjunction with renography in the evaluation of patients with
possible renovascular hypertension.10,11,13-16 Captopril is given
orally at a dose of 25 mg to 50 mg. Rapid absorption occurs with
peak blood levels at about one hour. Reduction of blood pressure is
maximal at 60 to 90 minutes after oral administration of an
individual dose. The duration of effect is dose-related.
Enalaprilat (Vasotec) is also one of the widely used ACE
inhibitors available in oral and parenteral forms. Its parenteral
form, in its active form, has made it convenient to administer the
medication at a standard dose without having to rely on the
patient's absorption kinetics to obtain a significant serum
In its active form, it is administered at a dose of 0.04 mg/kg
up to a maximum of 2.5 mg. Vasotec results in the reduction of both
supine and standing systolic and diastolic blood pressure, usually
with no orthostatic component, within 15 minutes after the
administration of an individual dose. The duration of effects also
is dose-related. The earlier onset
of action of Vasotec significantly shortens the duration of the
Patient selection criteria Blaufox et al have suggested that
screening for renovascular hypertension is not cost-effective at a
prevalence rate of less than 30%.29 To ensure that the prevalence
rate is greater than 30%, patients must possess certain
characteristics, which were established by the Working Party Group
for Patient Selection and Preparation during the Captopril Renogram
Consensus Conference.30,31 These characteristics include the
1. Well-documented, recent-onset hypertension, especially if the
diastolic blood pressure is greater than or equal to 105 mm Hg.
2. Known long-standing and well-controlled hypertension that
becomes refractory to an existing regimen when there is no other
explanation for the resistance to treatment.
3. Clinical evidence of generalized vascular disease (i.e.,
peripheral vascular disease, cerebrovascular disease).
4. Hypertension and abdominal bruits.
5. Hypertension and an elevated
serum creatinine when no other etiology can be found to explain
6. Patients under the age of 25 who develop moderate or severe
hypertension (i.e., diastolic blood pressure of greater than or
equal to 105 mm Hg), especially if they are white and not
7. Refractory hypertension on an adequate three-drug
antihypertensive regimen when no other etiology can
8. Hypertension associated with new or more severe renal failure
when treated with ACE inhibitors.
Other types of patients in whom ACE inhibitor renography may be
of help, according to the Report of the Working Party Group for
Patient Selection and Preparation, include the following.
1. Significant renal insufficiency without hypertension when no
other etiology for the impaired renal function may be found.
2. Hypertension after a renal transplant.
3. Mild renal insufficiency with or without significant
hypertension, with vascular disease elsewhere.
4. New or more severe renal failure while on ACE inhibitors.
At Loyola University Medical Center, we routinely obtain a
medication history. If the patients are on any ACE inhibitors, the
referring physicians are requested to withhold ACE inhibitors for
at least 72 hours prior to the day of the examination. Other forms
of antihypertensive medications may be prescribed for the
One hour prior to the initial baseline study, the patients are
asked to take in 10 cc/kg of water orally. Patients should void
immediately prior to the study. Images are obtained with a large
field of view gamma camera equipped with a low-energy all-purpose
collimator. The system is peaked at 140 keV with a 20% window.
With the patient supine and the camera positioned posteriorly, 5
mCi of Tc-99m MAG-3 (Mallinckrodt) is injected intravenously.
Analog images are acquired dynamically at 180 seconds per frame for
7 frames (21 minutes). Dynamic computer acquisition is done at 15
seconds per frame, 84 frames, in a 64 x 64 word matrix.
Four hours later, an IV line of 0.9% NaCl solution at K/O is
inserted. The patients were then attached to a blood pressure
monitor and readings were obtained every 5 minutes for 30 minutes
and every 15 minutes for the rest for the duration of the patients'
stay in the department.
After obtaining a baseline blood pressure reading, enalaprilat
(Vasotec) at a dose of 0.04 mg/kg is administered IV to a maximum
of 2.5 mg over 5 minutes. The patients are observed for 10 to 15
minutes before a repeat Tc-99m MAG-3 renogram is performed with the
same dose and technique as the baseline study. The IV line remains
in place until the completion of the study.
The studies are categorized as normal or abnormal renograms with
no evidence of unilateral renal artery stenosis, and abnormal study
with evidence of renal artery stenosis. Normal studies were
described as those having normal baseline renograms with no
significant difference in the post-Vasotec renogram. Abnormal
renograms with no evidence of unilateral renal artery stenosis were
described as having abnormal baseline renograms that do not show
any significant difference post Vasotec.
An abnormal study with evidence of renal artery stenosis shows a
significant difference in renal function between the baseline and
the post-Vasotec reno-
grams. The post-Vasotec study shows a delay in the time to peak
activity and/or an impairment in the excretory (third) phase of the
renogram of the affected kidney.27,32-35
Case 1-A 64-year-old hispanic female was referred for Vasotec
renal scan because of uncontrolled hypertension. The patient has
been hypertensive for the past year and has been on multiple
antihypertensive medications. Presently, the patient is on
amlodepine (Norvasc®). Baseline blood pressure at the time of the
study was 168/74. Fifteen minutes after the IV administration of
Vasotec, the blood pressure decreased to 130/72. At the end of the
study, the blood pressure was 126/80. At no time during the study
did the patient complain of any hypotensive symptoms. The renogram
curves (figure 1) of the patient, pre- and post-Vasotec, are
Case 2-A 74-year-old black male was referred for a Vasotec renal
scan because of hypertension. The patient has been a known
hypertensive for the past five years and has been on diuretics and
calcium channel blockers. The patient's blood pressure recently
became difficult to control with his usual medications. His
baseline blood pressure was 192/108. At 15 minutes post Vasotec
administration, the blood pressure was 132/68. At the end of the
study, his blood pressure was 112/67.
The patient was asymptomatic and did not manifest any signs of
hypotension. The pre- and post-Vasotec renogram curves (figure 2)
show a significant alteration in renal function of the left kidney
in the post-Vasotec study when compared with the baseline study.
The patient eventually had a renal angioplasty and his hypertension
Based on the captopril data, ACE inhibitor renography is safe
and effective. Vasotec offers the advantage of IV administration
with rapid predictable effects. Although Vasotec renal scintigraphy
is a good noninvasive screening procedure, strict adherence to the
guidelines of patient selection needs to be imposed by referring
physicians so as to ensure a prevalence rate of greater than 30% in
the screened patients for renovascular hypertension; this is so
that the test is cost-effective for screening patients for possible
renal artery stenosis. AR
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