Effect of captopril on 99mTc-diethylenetriaminepentaacetic acid renograms in two-kidney, one clip hypertension

In an effort to improve on the noninvasive detection of renal artery stenosis, we investigated the effect of angiotensin converting enzyme inhibition on computer-assisted 99mTc-diethylenetriaminepentaacetic acid (DTPA) renal flow studies in a canine model of two-kidney, one clip hypertension and compared these findings with clearances of inulin and p-aminohippuric acid in the stenotic and contralateral kidney before and after converting enzyme inhibition. The 99mTc-DTPA renal flow study with the converting enzyme inhibitor captopril (1.5 mg/kg bolus with 1.5 mg/min infusion) showed an increased sensitivity in the detection of unilateral renal artery stenosis over the use of the 99mTc-DTPA study alone. Captopril induced striking alterations that were most evident in the 15-minute 99mTc-DTPA renal flow study, in which all nine curves exhibited severely blunted uptake and excretion of the radionuclide. These changes were reversed during a recovery study without converting enzyme inhibition and were not seen when blood pressure was lowered with nitroprusside to a level similar to that observed during converting enzyme inhibition. The changes shown by the 99mTc-DTPA study during converting enzyme inhibition correlated with a decrease in the glomerular filtration rate of the stenotic kidney. Captopril infusion significantly decreased the glomerular filtration rate of the stenotic kidney (16.0 +/- 3.1 vs 11.0 +/- 2.5 mg/min, p less than 0.03) but not of the contralateral kidney (32.4 +/- 2.6 vs 28.4 +/- 2.8 mg/min).(ABSTRACT TRUNCATED AT 250 WORDS)     

Ramipril for hypertension secondary to renal artery stenosis. Changes in blood pressure, the renin-angiotensin system and total and divided renal function

The converting enzyme inhibitor, ramipril, 20 mg once daily, was given to 3 hypertensive patients with unilateral renovascular disease. At 1 month, 24 hours after the last dose of ramipril, blood pressure, plasma angiotensin II and converting enzyme activity remained low, and active renin and angiotensin I high. There was no tendency for converting enzyme inhibition to be overcome during 1 month of ramipril therapy. Ramipril caused slight increases in serum potassium and urea, no change in serum creatinine and no consistent changes in the renal vein renin ratio. Ramipril caused little change in renal plasma flow on the stenotic side, but filtration fraction was reduced in 2 patients. There was no serious deterioration in total or individual glomerular filtration rate during ramipril therapy. The drug was well tolerated and there were no serious side effects. Ramipril, given once daily, is likely to be effective in controlling hypertension with renal artery stenosis.     

Unilateral stent implantation for renal function in bilateral atherosclerotic renovascular hypertension--a case report

Renal artery stenting improves or preserves renal function in patients with bilateral renovascular disease and chronic renal insufficiency. An 80-year-old male was admitted to the hospital for elevated blood pressure accompanied by congestive heart failure. He had renal insufficiency and severe hypertension secondary to bilateral atherosclerotic renal artery stenosis. Unilateral renal artery stenting in the left kidney resulted in the recovery of renal function, whereas renal artery stenting in the right kidney was technically difficult due to a tortuous aorta. After the left unilateral stent implantation, the serum creatinine concentration decreased from 2.0 to 1.3 mg/dL, and control of his blood pressure required fewer antihypertensive drugs, namely a calcium antagonist, an angiotensin-converting enzyme inhibitor, and diuretics. Fifteen months after stenting, renal scintigraphy demonstrated improved function of the right kidney, despite severe renal artery stenosis, as well as improved function of the left kidney. Renal angioplasty or stenting should be attempted in bilateral atherosclerotic renovascular hypertension with renal insufficiency, even though it may only be successful unilaterally.     

Renal scintigraphic captopril test in the diagnosis of renovascular hypertension

Angiotensin converting enzyme (ACE) inhibitor-induced renal failure has been reported in bilateral renal artery stenosis and in stenosis in solitary kidneys, but not in unilateral renal artery stenosis. In these patients, however, a functional impairment of the kidney ipsilateral to the stenosis can often be detected after ACE inhibition by scintigraphic techniques employing glomerular radionuclide tracers like 99mTc-diethylenetriamine pentaacetic acid (DTPA). Dynamic renal scintigraphy with 99mTc-DTPA before and 1 hour after administration of captopril, 25 mg (renal scintigraphic captopril test; RSCT), was performed in a selected series of 39 hypertensive subjects with suspected renovascular hypertension. Changes in glomerular filtration rate induced by captopril on the individual kidney were estimated by assessing the early (120-180 seconds) DTPA uptake by the kidney. Values were expressed as the ratio between the kidney with the lower uptake and the contralateral one in 34 patients and as the ratio of the kidney counts to the injected dose in five patients with solitary kidneys, aortic coarctation, or both. Compared with precaptopril values, postcaptopril uptake decreased markedly in 14 subjects (-62.42 +/- 30.94 [SD]%; range, -25 to -100%) and decreased modestly or even increased in the other 25 (+0.57 +/- 9.83%; range, +28 to -13%). Of the 14 subjects considered to be RSCT-positive diagnostic workup revealed either established (10) or strongly suspected (2) renal artery stenosis in 12 and aortic coarctation in 2 subjects. In another patient with established renovascular hypertension, results of the RSCT were negative when performed in the supine position but became positive when repeated in the sitting position.(ABSTRACT TRUNCATED AT 250 WORDS)     

Lack of effect of percutaneous transluminal renal angioplasty on nocturnal hypotension in renovascular hypertensive patients

OBJECTIVE: To investigate whether nocturnal blood pressure fall is blunted in renovascular hypertension and can therefore be used as a diagnostic criterion for this condition. METHODS: In 14 renovascular hypertensive patients (age 43.8+/-2.1 years, mean+/-SEM, clinic blood pressure 173.6+/-3.7 mmHg systolic and 109.0+/-2.0 mmHg diastolic) and in 14 age- and blood pressure-matched essential hypertensive controls 24 h ambulatory blood pressure was measured after washout from drug treatment, during angiotensin converting enzyme inhibitor treatment and, in renovascular hypertension, also after percutaneous transluminal renal angioplasty. RESULTS: The 24 h average systolic and diastolic blood pressures were 146.4+/-5.7 and 97.5+/-3.6 mmHg in renovascular and 144.3+/-1.2 and 98.0+/-2.2 mmHg in essential hypertensive patients. The angiotensin converting enzyme inhibitor treatment reduced 24 h average systolic and diastolic blood pressures by 8.5% and 9.7% in the renovascular and by 8.3% and 10.8% in the essential hypertensive group. Greater systolic and diastolic blood pressure reductions (-18.2% and -18.1%) were observed in renovascular hypertensive patients after percutaneous transluminal renal angioplasty. Blood pressure fell by about 10% during the night and the fall was similar in renovascular and in essential hypertensive patients. In the former group, nocturnal hypotension was similar after washout, during angiotensin converting enzyme inhibitor treatment and after percutaneous transluminal renal angioplasty. Similar results were obtained for nocturnal bradycardia. CONCLUSIONS: Nocturnal blood pressure fall is equally manifest in renovascular and essential hypertension. The removal of the renal artery stenosis and blood pressure normalization do not enhance this phenomenon. Nocturnal hypotension seems therefore to be unaffected by renovascular hypertension.     

Enalapril in the Treatment of Renovascular Hypertension

Enalapril, an angiotensin converting enzyme (ACE) inhibitor, was given to 12 patients with renovascular hypertension: To five of them as a single drug after discontinuing other medications, and to seven patients as a substitute for one of their previous medications. The drug proved effective in controlling hypertension in all patients. Flushing and palpitations occurred in two of them, one of whom also showed a rise in creatinine and mild hyperkalemia. Two patients who had developed side effects while on captopril (renal deterioration in one, and severe rash in the other) tolerated enalapril well. Enalapril effectively reduced the blood pressure in the one patient with bilateral renal artery stenosis without causing renal failure.     

Long-term follow-up of renal artery stenting in an Australian population

BACKGROUND: Renal artery stenosis comprises both atherosclerotic renovascular disease and fibromuscular dysplasia, and may be associated with refractory hypertension, acute 'flash' pulmonary oedema and renal failure. The long-term clinical effects of renal artery stenting remain unclear. AIM: To assess the procedural and long-term safety and efficacy of renal artery stenting and its effect on blood pressure, antihypertensive medication usage and serum creatinine. METHODS: All patients referred for renal artery stenting at our institution between September 1997 and December 2003 were entered into a prospectively collected database. Systolic and diastolic blood pressure, number of antihypertensive medications, serum creatinine and estimated glomerular filtration rate (eGFR) were recorded. Patients were followed-up at least six months post-procedure. RESULTS: Eighty-nine patients underwent renal arteriography, with 110 stents deployed in 102 lesions. The procedural success rate was 99% with no procedural mortality. There were two cases of peri-procedural haemorrhage and one of sepsis. One patient developed renal and peripheral atheroemboli. FOLLOW-UP: Mean follow-up was 28 months (range 6 months-7 years). Eight patients were lost to follow-up. There were nine deaths with a mean time to death of 20.7 months (range 12 months-3 years). There was a highly statistically significant fall in systolic blood pressure (BP) from 161.7+/-29.5 mmHg pre-procedure to 138.7+/-17.9 mmHg at long-term follow-up post-procedure (p<0.0001). The clinical restenosis rate was 6.2%. Renal function and eGFR remained stable and there was a borderline significant decrease in the number of antihypertensive medications used (p=0.05). CONCLUSION: Renal artery stenting is safe and appears effective for the treatment of clinically significant renal artery stenosis.     

Effect of angiotensin on renal transport of sodium in renovascular hypertension

Eleven patients with renovascular arterial hypertension were studied, 9 of whom had unilateral renal artery stenosis and 2 bilateral renal artery stenosis.

Angiotensin increased sodium excretion in the contralateral kidney and did not change it in the stenotic one.

In bilateral stenosis angiotensin increased sodium excretion significantly in both kidneys.

The difference in response to angiotensin between patients with unilateral stenotic kidney and those with bilateral stenosis is apparently unrelated to arterial blood pressure distal to the arterial stenosis.     

Rapid improvement of acute pulmonary edema with angiotensin converting enzyme inhibitor under hemodialysis in a patient with renovascular disease

A 71-year-old man with bilateral renovascular disease was admitted to Hamamatsu University hospital because of appetite loss and acute shortness of breath due to acute pulmonary edema (APE) with accelerated hypertension and renal failure. Hypertension and APE were controlled by an angiotensin converting enzyme inhibitor (ACEI) and four sessions of hemodialysis with reduction of 1.8 kg bodyweight. Renal function was later stabilized and the patient required no ACEI or hemodialysis. A trial of right renal angioplasty 1 month after admission failed and renal function deteriorated (serum creatinine 7.1 mg/dL) with accelerated hypertension, gain of bodyweight and APE. Even after four sessions of hemodialysis with adequate reduction of bodyweight, APE was not controlled, but it rapidly improved after administration of an ACEI, without major bodyweight change. As no apparent cardiac dysfunction was evident, APE might have been caused by a direct action of angiotensin II on hyperpermeability in pulmonary capillaries. Blocking of angiotensin II should be considered in such patients even after introduction of hemodialysis.     

Effects of converting enzyme inhibition on split renal function in renovascular hypertension

The effects of captopril on effective renal plasma flow and glomerular filtration rate were studied using a noninvasive radioisotopic method on individual kidneys in eight patients with renovascular hypertension and 12 patients with essential hypertension with various renin levels. Four patients with renovascular hypertension had unilateral while three had bilateral renal artery stenosis. The effective renal plasma flow and glomerular filtration rate were determined by using 131I-iodohippurate sodium and 99mTc-diethylenetriamine pentaacetic acid, respectively. Glomerular filtration rate and effective renal plasma flow were significantly reduced in the stenotic kidneys of patients with renovascular hypertension compared with values in nonstenotic kidneys (p less than 0.01). Treatment with captopril, 37.5 to 75 mg/day for 1 to 48 weeks, further reduced the glomerular filtration rate only in stenotic kidneys, and effective renal plasma flow increased in both kidney types. In two of the three renal hypertensive patients with bilateral renal artery stenosis, captopril produced a reversible azotemia that was unrelated to the fall in blood pressure, as evidenced by the lack of azotemia seen after a moderate blood pressure reduction induced by other antihypertensive medications. These results indicate that endogenous angiotensin II is essential in maintaining the glomerular filtration rate in stenotic kidneys and suggest that a reduction in glomerular filtration rate during captopril administration could indicate the presence of renal artery stenosis.     

Proteinuria in renovascular hypertension and the effects of renal angioplasty

In 46 patients with renovascular hypertension who underwent renal angioplasty, proteinuria (more than 150 mg/24 hours) was more pronounced than in patients with essential hypertension. The highest levels were seen in patients in whom 1 renal artery was totally occluded. There was no difference between patients with unilateral vs bilateral renal artery stenosis. Proteinuria could not be correlated with serum creatinine level, and in 28% of the patients with renovascular hypertension, proteinuria was present despite a normal creatinine level. Renal angioplasty produced a significant diminution in proteinuria when it resulted in a cure of the hypertension, but no diminution was achieved if blood pressure did not decrease.     

Atherosclerotic renal artery stenosis

Opinion statement The clinical diagnosis of renal artery stenosis relies on a high index of suspicion and confirmation by noninvasive imaging modalities. There are three distinct clinical syndromes associated with renal artery stenosis: renin-dependent hypertension, essential hypertension, and ischemic nephropathy. Clinical features that should heighten suspicion for renal artery stenosis include abrupt-onset or accelerated hypertension at any age, unexplained acute or chronic azotemia, azotemia induced by angiotensin-converting enzyme (ACE) inhibitors, asymmetric renal dimensions, and congestive heart failure with normal ventricular function. Patients with true renin-dependent (renovascular) hypertension are typically young or middle-age women with renal fibromuscular dysplasia (FMD). Initial therapy for renovascular hypertension associated with FMD is an ACE inhibitor; refractory hypertension responds readily to balloon angioplasty without stenting. Elderly patients with generalized atherosclerosis and hypertension often have atherosclerotic renal artery stenosis (ARAS); hypertension in these patients is usually not renin dependent (ie, essential hypertension). Hypertension alone, even if treated with multiple medications, is not a compelling indication for renal artery revascularization; these patients should be treated aggressively with antihypertensive medical therapy. Renal artery revascularization with stenting may be considered for refractory severe hypertension, and would be expected to improve blood control and modestly reduce medication requirements. Renal revascularization rarely cures hypertension in patients with ARAS. Patients with ARAS, hypertension, and end-organ injury should be considered for renal revascularization. Manifestations of end-organ injury include nonischemic pulmonary edema; hypertensive crisis associated with acute coronary syndrome, aortic dissection, or neurologic impairment; and renal insufficiency. Ischemic nephropathy is best treated before the development of advanced renal failure. The best candidates for revascularization are those with baseline serum creatinine less than 2.0 mg/dL, bilateral renal artery stenosis, normal renal resistive indices, no proteinuria, and one or more manifestations of end-organ injury. In these patients, renal revascularization is best accomplished by stenting, although surgical revascularization may be considered in patients with concomitant severe aortic aneurysmal or occlusive disease.     

Clinical benefit of renal artery angioplasty with stenting for the control of recurrent and refractory congestive heart failure

Renal artery stenosis (RAS) may cause hypertension, azotemia, episodes of flash pulmonary edema and congestive heart failure. Renal artery angioplasty and stenting was performed in 207 patients from 1991 to 1997. Thirty-nine of these patients (19%) underwent renal artery stenting for the control of recurrent episodes of congestive heart failure and flash pulmonary edema. All patients had angiographic evidence of severe (>70%) bilateral RAS (n = 18) or severe RAS to a solitary functioning kidney (n = 21). Sixteen patients (41%) were male and 23 (59%) were female, mean age 69.9 years (range 50-85 years). Of the 18 patients with bilateral RAS, 12 (66.6%) underwent bilateral stenting. Mean blood pressure decreased from 174/85 +/- 32/23 mmHg to 148/72 +/- 24/14 mmHg (p < 0.001). Mean number of blood pressure medications decreased from 3 +/- 1 to 2.5 +/- 1 (p = 0.006). Twenty-eight patients (71.8%) had improvement in blood pressure control. The mean serum creatinine decreased from 3.16 +/- 1.61 to 2.65 +/- 1.87 (p = 0.06). Six of 39 patients (15.4%) used angiotensin converting enzyme (ACE) inhibitors prior to stenting whereas 19 of 39 patients (48.7%) used ACE inhibitors poststenting (p = 0.004). Twenty of 39 patients (51.4%) demonstrated improvement in serum creatinine, 10 of 39 patients (25.6%) had stabilization of serum creatinine and nine of 39 patients (23%) demonstrated worsening. The number of hospitalizations due to congestive heart failure in the year preceding renal artery stenting was 2.4 +/- 1.4 and poststenting was 0.3 +/- 0.7 (p < 0.001). The New York Heart Association Functional Class decreased from 2.9 +/- 0.9 prestenting to 1.6 +/- 0.9 poststenting (p < 0.001). Thirty of 39 patients (77%) had no hospitalizations for congestive heart failure during a mean follow-up period of 21.3 months. Nine patients expired during the course of follow up; eight of the nine patients died within the first year after renal artery stenting. Renal artery stenting decreased the frequency of congestive heart failure, flash pulmonary edema, and the need for hospitalization in most patients. Blood pressure was markedly improved in the majority of patients with improved or stabilized renal function. Evaluation for RAS is important in hypertensive patients who present with recurrent congestive heart failure or flash pulmonary edema.     

Renovascular hypertension identified by captopril-induced changes in the renogram

Radioisotope renography was performed in 21 patients with hypertension and unilateral renal artery stenosis with and without premedication with 25 mg of captopril, and the results were compared with the effect of percutaneous transluminal angioplasty on the blood pressure, assessed 6 weeks after angioplasty. Angioplasty caused a considerable decrease in blood pressure in 15 of the 21 patients. In 12 of these 15 patients, captopril induced changes in the time-activity curves of the affected kidney only, suggesting deterioration of the excretory function of that kidney, while the function of the contralateral kidney remained normal. After angioplasty the asymmetry in the time-activity curves diminished despite identical pretreatment with captopril. Such captopril-induced unilateral impairment of the renal function was not seen in the six patients with unilateral renal artery stenosis whose blood pressure did not change after percutaneous transluminal angioplasty or in 13 patients with hypertension and normal renal arteries. The functional impairment of the affected kidneys was characterized by a decrease of 99mTc-diethylenetriamine pentaacetic acid uptake and a delay of 131I-hippurate excretion, while the 131I-hippurate uptake remained unaffected. These data are in agreement with a reduced glomerular filtration rate and diuresis during preservation of the renal blood flow, changes that can be expected after converting enzyme inhibition in a kidney with low perfusion and an active, renin-mediated autoregulation of the glomerular filtration rate. These data suggest that functional captopril-induced unilateral changes, shown by split renal function studies with noninvasive gamma camera scintigraphy, can be used as a diagnostic test for renovascular hypertension caused by unilateral renal artery stenosis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Furosemide augments the effects of captopril on nuclear studies in renovascular stenosis

Captopril facilitates detection of unilateral renovascular hypertension by selectively reducing glomerular filtration rate in affected kidneys. To determine if volume depletion augments this response, we compared the effects of captopril, furosemide, and combined furosemide plus captopril on individual kidney computer-derived clearances of 99mTc-diethylenetriamine pentaacetic acid (DTPA) and [131I]o-iodohippurate in two-kidney, one clip Goldblatt hypertensive rats and normal controls. In clipped kidneys, captopril reduced DTPA clearance significantly from baseline (from 0.31 +/- 0.02 to 0.19 +/- 0.04 ml/min/100 g; p less than 0.02) whereas furosemide alone had no effect (0.28 +/- 0.03 ml/min/100 g). Combined furosemide plus captopril further reduced clipped kidney DTPA clearance to a level significantly less than captopril alone (0.10 +/- 0.02 ml/min/100 g; p less than 0.02). Clipped kidney o-iodohippurate clearance was not changed from baseline by any treatment. In contralateral unclipped and normal kidneys, DTPA clearance did not decline from baseline following either captopril or furosemide plus captopril treatment. Since the dose of captopril used (3 mg/kg by intraperitoneal injection) did not reduce systolic blood pressure of hypertensive rats significantly, these changes probably reflect intrarenal rather than systemic hemodynamic effects of converting enzyme inhibition and are consistent with the hypothesis that captopril interferes with glomerular filtration in stenotic kidneys by reducing efferent arteriolar vascular resistance. Prior volume depletion accentuates the effect of captopril on stenotic kidney glomerular filtration rate, providing improved functional discrimination of stenotic kidneys from contralateral unclipped and normal kidneys. These results indicate that furosemide-induced volume depletion may increase the diagnostic sensitivity of captopril-enhanced 99mTc-DTPA renography in the detection of unilateral renovascular hypertension.     

Reversible renal failure after combined treatment with enalapril and frusemide in a patient with congestive heart failure

A patient with congestive heart failure and moderate renal insufficiency developed severe reversible non-oliguric renal failure while on frusemide and enalapril. Renal failure developed when enalapril was given in the presence of pronounced sodium depletion. When positive sodium balance was restored the plasma creatinine concentration began to fall while angiotensin converting enzyme inhibition remained effective and blood pressure was stable. These observations suggest that the degree of sodium depletion plays an important role in the tendency for angiotensin converting enzyme inhibitors to induce renal failure in patients with congestive heart failure and moderate renal insufficiency. Restoration of a positive sodium balance promotes the recovery of renal function after the combined administration of angiotensin converting enzyme inhibitors and diuretics.     

The effect of percutaneous dilatation of renal arterial stenosis on captopril renography in hypertension

BACKGROUND: The clinical effects of percutaneous transluminal renal artery angioplasty (PTRA) in patients with renal vascular stenosis and hypertension is controversial. METHODS: We consecutively recruited all 23 patients referred for evaluation of renovascular hypertension that eventually underwent unilateral PTRA, to be investigated with captopril MAG3 renography (CR), both before and after the endovascular procedure. Data were evaluated on an intention-to-treat basis. RESULTS: We found that the relative MAG3 clearance of the stenotic kidney increased (from 29.9+/-14% to 35.1+/-14%, p=0.01) and that the creatinine levels fell following the intervention (from 110+/-19 to 99+/-17 micromol/l, p=0.0003). Blood pressure levels were also lowered (from 173+/-32/93+/-17 to 158+/-31/86+/-15 mmHg, p<0.006) while the mean number of anti-hypertensive drugs was unchanged following PTRA (2.9+/-1.4 before and 2.8+/-1.3 drugs after the intervention, respectively, p=0.6). CONCLUSION: This prospective trial showed statistically significant improvements of individual kidney function as measured by CR and blood pressure in subjects with suspected renovascular hypertension treated with PTRA. Although the endovascular procedure was found to be safe, the magnitude of the absolute improvements was rather modest.     

Reversible renal failure after combined treatment with enalapril and frusemide in a patient with congestive heart failure.

A patient with congestive heart failure and moderate renal insufficiency developed severe reversible non-oliguric renal failure while on frusemide and enalapril. Renal failure developed when enalapril was given in the presence of pronounced sodium depletion. When positive sodium balance was restored the plasma creatinine concentration began to fall while angiotensin converting enzyme inhibition remained effective and blood pressure was stable. These observations suggest that the degree of sodium depletion plays an important role in the tendency for angiotensin converting enzyme inhibitors to induce renal failure in patients with congestive heart failure and moderate renal insufficiency. Restoration of a positive sodium balance promotes the recovery of renal function after the combined administration of angiotensin converting enzyme inhibitors and diuretics.     

Renal Considerations in Geriatric Patients With Heart Disease

Renal and electrolyte complications occur commonly in elderly patients with heart disease. Renal function declines with age. A seemingly normal serum creatinine level in the geriatric patient often represents a creatinine clearance of 60 ml/min or less. It is important to measure or estimate the creatinine clearance in an older patient with a borderline high or elevated serum creatinine level before administering renally excreted drugs. The Cockcroft and Gault formula is recommended for estimating the creatinine clearance in such patients. Impaired renal function can also predispose to drug-induced hyperkalemia in geriatric patients; the most common offending drugs are potassium chloride supplements, potassium-sparing diuretics, angiotensin-converting enzyme inhibitors, digoxin, and nonsteroidal anti-inflammatory drugs. Elderly patients should be evaluated for renal artery stenosis if they have worsening of previously stable hypertension, new-onset hypertension, or progressive renal impairment on angiotensin-converting enzyme inhibitors. Risk factors and management guidelines for radiocontrast nephropathy in the elderly are also discussed.     

Effects of enalapril in heart failure: a double blind study of effects on exercise performance, renal function, hormones, and metabolic state

Several studies have shown symptomatic and haemodynamic improvement after the introduction of angiotensin converting enzyme inhibitors in patients with heart failure treated with diuretics. The concomitant long term effects of the new orally effective long acting angiotensin converting enzyme inhibitor, enalapril, on symptoms, exercise performance, cardiac function, arrhythmias, hormones, electrolytes, body composition, and renal function have been further assessed in a placebo controlled double blind cross over trial with treatment periods of eight weeks. Twenty patients with New York Heart Association functional class II to IV heart failure who were clinically stable on digoxin and diuretic therapy were studied. Apart from the introduction of enalapril, regular treatment was not changed over the study period; no order or period effects were noted. Enalapril treatment significantly improved functional class, symptom score for breathlessness, and exercise tolerance. Systolic blood pressure was significantly lower on enalapril treatment. Echocardiographic assessment indicated a reduction in left ventricular dimensions and an improvement in systolic time intervals. In response to enalapril, the plasma concentration of angiotensin II was reduced and that of active renin rose; plasma concentrations of aldosterone, vasopressin, and noradrenaline fell. There were significant increases in serum potassium and serum magnesium on enalapril. Glomerular filtration rate measured both by isotopic techniques and by creatinine clearance declined on enalapril while serum urea and creatinine rose and effective renal plasma flow increased. Body weight and total body sodium were unchanged indicating that there was no overall diuresis. There was a statistically insignificant rise in total body potassium, though the increase was related directly to pretreatment plasma renin (r = 0.5). On enalapril the improvement in symptoms, exercise performance, fall in plasma noradrenaline, and rise in serum potassium coincided with a decline in the frequency of ventricular extrasystoles recorded during ambulatory monitoring. Adverse effects were few. In patients with heart failure, enalapril had a beneficial effect on symptoms and functional capacity. The decline in glomerular filtration rate on enalapril may not be beneficial in early heart failure.