Active and inactive renin after a single dose of captopril in hypertensive patients

In 25 hypertensive patients (15 with renal artery stenosis and 10 with essential hypertension), captopril, in a single 12.5 mg dose, caused a prompt decrease in arterial pressure without changing the heart rate. Plasma active and trypsin-activated renin significantly increased, whereas inactive renin and plasma aldosterone decreased. The plasma active/ inactive renin ratio was also increased, suggesting that captopril, together with a release of active renin, may induce an in vivo activation of inactive renin.No correlations were found between blood pressure changes and both pretreatment and captopril-induced variations of active, inactive and trypsin-activated renin or the active/inactive ratio. However, the percent decrease in mean arterial pressure was significantly related to the increase in the active/inactive renin ratio in a group of patients whose blood pressure was brought to normal (r = ?0.78; p < 0.001). This finding suggests the possibility that vasodilating substances, in addition to inhibiting angiotensin II formation, might play some role both in exerting a full effect of captopril on blood pressure and in triggering the in vivo mechanisms of inactive renin activation.     

Effects of prolonged and brief infusions of noradrenaline on arterial pressure and on the plasma concentrations of active renin, angiotensin II, aldosterone and potassium

Conscious male beagle dogs were given constant intravenous infusions of noradrenaline for 14 days, four receiving 125 ng/kg/min and four 250 ng/kg/min. Before, during and after these infusions dose-response studies were done in which additional noradrenaline was infused at 500, 1000 and 2000 ng/kg/min, each rate for 1 h. Blood samples were taken before and during infusions for measurement of haematocrit and plasma concentrations of noradrenaline, active renin, angiotensin II, aldosterone, sodium and potassium. Fourteen-day infusion of noradrenaline at 125 ng/kg/min did not raise blood pressure significantly though infusion at 250 ng/kg/min did, but for the first week of infusion only. Heart rate decreased significantly at both rates. Arterial pressure fell markedly and significantly on stopping infusion. Mean plasma concentrations of renin, angiotensin II and aldosterone tended to be lower during prolonged infusion of noradrenaline, but only the fall of renin during the second week was significant in one group of dogs. Noradrenaline at higher rates significantly raised blood pressure and increased plasma concentrations of renin and angiotensin II. Plasma aldosterone concentration did not rise significantly, perhaps because plasma potassium concentration decreased; in support of this theory changes of plasma aldosterone correlated with changes of plasma potassium but not with changes of angiotensin II. The rise in arterial pressure during dose-response studies was related to the increase of plasma noradrenaline. Prolonged infusion of noradrenaline did not alter the dose-response relation between plasma noradrenaline concentration and arterial pressure.     

Cardiovascular reflexes during long-term converting enzyme inhibition and sodium depletion: The response to tilt in hypertensive patients

The reflex hemodynamic and humoral response to postural change during long-term renin-angiotensin blockade (captopril) was assessed in sodium-depleted hypertensive patients. Orthostatic hypotension was not observed with head-up tilt or repeated pressure recordings. During tilt, a reflex increase of heart rate occurred (76 ± 2 to 98 ± 4 bpm, p < 0.001). Home recordings demonstrated only minor changes in blood pressure with standing. To evaluate these observations, hemodynamic studies were performed during tilt at three stages of therapy: control, administration of captopril, and administration of captopril plus diuretic. With tilt, no orthostatic hypotension was noted at all three stages of therapy, despite similar peripheral pooling (?22 percent cardiac index). Maintenance of blood pressure was due to reflex increase of heart rate (44, 45 and 38 percent) and systemic resistance (34, 38 and 37 percent). The response to tilt of plasma renin activity was modified by drug therapy, but not completely blocked. This study indicated that long-term converting enzyme inhibition and sodium depletion were safe and did not appreciably blunt the cardiovascular reflexes responsible for prevention of orthostatic hypotension.     

Use of Captopril in the Diagnosis of Renal Hypertension

Abstract: 1 . The effects of a single 25 mg oral dose of captopril on blood pressure, heart rate and circulating renin, angiotensin I, angiotensin II, bradykinin and catecholamine levels were examined in untreated patients with essential (n = 10, Group I), accelerated (n = 6, Group II) and renal hypertension (n = 8, Group III) studied on a normal sodium diet .
2 . Mean blood pressure fell only slightly in Group I patients, (113 ± 3 to 109 ± 3 mmHg at 60 minutes) but a greater fall was observed in Group II (153 ± 8 to 135 ± 11 mmHg) and a marked fall in Group III, (136 ± 3 to 114 ± 5 mmHg). There were no significant changes in heart rate in any group .
3 . Plasma angiotensin II levels were significantly reduced 30 minutes after captopril in all three groups and returned toward resting values after four hours. The falls in plasma angiotensin II levels were accompanied by reciprocal increases in blood angiotensin I and plasma renin, but blood bradykinin and plasma catecholamine concentrations remained unchanged .
4 . Resting plasma renin levels showed considerable overlap in the three groups and the mean renin values were not significantly different in the three groups. After captopril a marked rise in plasma renin concentration (>2.5 ng/ml/hr) was observed in seven patients in Group III, including all six patients with renovascular disease. In contrast, none of the patients with essential hypertension and only one patient with accelerated hypertension had such an increase. Determination of the acute renin and blood pressure responses to converting enzyme inhibition with a single oral dose of captopril appears to be useful in identifying patients with renovascular hypertension .     

Cardiovascular regulation during angiotensin converting enzyme inhibition with captopril in diabetes-associated hypertension

Diabetes-associated hypertension is accompanied by high levels of body sodium and cardiovascular hyper-reactivity to noradrenaline. Captopril, a promising drug for the treatment of hypertension in diabetics, may influence sodium metabolism and adrenergic pathways. This possibility was investigated in 11 patients with non-azotaemic diabetes mellitus and hypertension, studied after a 3-week placebo phase and after an 8-week phase of captopril treatment (50-100 mg/day). Blood pressure, exchangeable body sodium, blood volume, plasma renin activity, angiotensin II (Ang II), aldosterone, catecholamine levels and the pressor reactivity to infused Ang II or noradrenaline were measured. Compared with placebo, captopril caused a significant decrease in arterial pressure and stimulation of plasma renin activity. Exchangeable sodium, blood volume, plasma Ang II, aldosterone, noradrenaline and adrenaline levels, the pressor and aldosterone responsiveness to infused Ang II and the pressor response to infused noradrenaline (alone or combined with atropine) were not modified. These findings suggest that in hypertensive diabetics angiotensin converting enzyme inhibition causes a marked decrease in blood pressure. The mechanism of action is unrelated to changes in body sodium or noradrenergic-dependent pressor reactivity. In the stable phase of therapy, Ang II-dependent pathways are left unaltered when captopril is administered twice a day.     

Effect of captopril and aprotinin on inactive renin

Inactive renin (prorenin) was measured in plasma from untreated hypertensive patients after acute (60 min) administration of the angiotensin I converting enzyme inhibitor captopril, after 4 weeks of treatment with captopril, and after an acute infusion of the protease inhibitor aprotinin. Inactive renin was unchanged during acute captopril therapy despite a 4-fold increase in active renin. In contrast, after 4 weeks of treatment with captopril, inactive renin had increased 2-fold and active renin was also elevated, but to a greater degree (6-fold). Active renin was significantly suppressed by the aprotinin infusion, to about 25%, but the inactive plasma renin level was apparently unchanged. These studies demonstrate that the time course of the responses of active and inactive plasma renins are different; the inactive renin level seems to change more slowly than does active renin in response to the same stimulus. The results also show that a neutral serine protease inhibitor can rapidly reduce the circulating level of active renin. This observation is consistent with the possibility, but does not prove it, that a kallikrein-like enzyme normally activating prorenin was inhibited by aprotinin.     

Effects of a single administration of captopril on hemodynamics and serum angiotensin converting enzyme activity, plasma renin activity and plasma aldosterone concentration in hypertensive patients

Hemodynamic responses and behaviors of the renin-angiotensin-aldosterone system to a single administration of captopril (50 mg) were studied in 16 hypertensive patients (essential hypertension, n = 10; renovascular hypertension, n = 3; primary aldosteronism, n = 2; Cushing's syndrome, n = 1). In 10 essential hypertensive patients, the immediate blood pressure reduction caused by decreased total peripheral resistance after the administration of captopril was observed without changes of cardiac output and heart rate. Serum angiotensin converting enzyme activity and plasma aldosterone concentration significantly decreased, whereas plasma renin activity significantly elevated 2 hours after the administration of captopril. The close relationship between the pretreatment value of plasma renin activity and the maximum decrease in mean blood pressure in 16 hypertensive patients suggests that the depressor response to a single administration of captopril could evaluate the degree of angiotensin II dependency in the maintenance of high blood pressure in various types of hypertension.     

Conversion of inactive renin to active renin following acute angiotensin converting enzyme inhibition in essential hypertension and renovascular hypertension

The physiological role of inactive renin, especially the question of whether and how a conversion to active renin takes place in vivo, remains controversial. In order to show the dynamic alterations from inactive to active renin following acute ACE-inhibition, both forms of renin were investigated in both renal veins and the peripheral circulation of 20 patients with essential hypertension and 20 patients with renovascular hypertension before and 1 h after 25 mg of captopril. Active and inactive renin were determined indirectly as plasma renin activity (PRA, unit: ng/ml x h). In vitro activation of inactive renin was achieved with trypsin (1 mg/ml plasma), followed by a further determination of PRA (= total renin). Subtraction of the active renin from the total renin yields the amount of inactive renin. In patients with essential hypertension, the mean values of active renin increase equally in both renal veins (1.4 and 1.3 before, 1.9 and 1.8 after captopril) and the peripheral circulation (0.9 and 1.3) (p less than 0.002), whereas the inactive renin decreases correspondingly. Renal veins: 7.6 and 8.2 before, 7.2 and 7.6 after captopril; peripheral circulation: 7.7 before and 7.0 after captopril (p less than 0.05). In all patients with renovascular hypertension, there is basally a marked lateralization of active renin (6.4 vs 3.5; p less than 0.01) and inactive renin (20.5 and 18.9, p less than 0.03) towards the side of the ischemic kidney. After captopril, the values for total renin and active renin increase (p less than 0.001), and the side difference for active renin becomes still more pronounced (33.0 vs 14.2; p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of the Calcium Antagonist Felodipine on the Sympathetic and Renin-Angiotensin-Aldosterone Systems in Essential Hypertension

ABSTRACT Studies were performed in 10 male patients with untreated essential hypertension, WHO grade I-II, aged 25–62 years, to explore the acute (single dose) and long-term (8 weeks) effects of felodipine on sympathetic activity—evaluated by plasma and urinary catecholamines—as related to blood pressure, heart rate and the activity in the renin-angiotensin-aldosterone system. The patients were hospitalized for 8 (acute) and 6 (long-term) days and were maintained on a standardized daily intake of sodium (150 mmol), potassium (75 mmol) and water (2500 ml). Acute felodipine administration (10 mg) significantly reduced blood pressure and increased heart rate. Plasma and urinary noradrenaline, plasma renin activity and angiotensin II increased, whereas plasma and urinary adrenaline, dopamine, aldosterone and plasma vasopressin were unaltered. Long-term felodipine treatment, 10 mg twice daily, reduced blood pressure to a similar extent as acute felodipine administration, but heart rate was not significantly changed. Plasma noradrenaline 3 and 12 hours after the last dose and urinary noradrenaline were increased, whereas plasma and urinary adrenaline and dopamine were unchanged. Plasma renin activity and angiotensin II were increased 3 hours, but unchanged 12 hours after the last dose. Plasma aldosterone was unchanged but urinary aldosterone increased. Plasma vasopressin was unchanged. The changes in plasma noradrenaline as related to blood pressure, heart rate, plasma renin activity and angiotensin II during long-term felodipine treatment may reflect decreased cardiac and renal β-adrenoceptor-mediated responses. Increased renal clearance of aldosterone could partly explain the unaltered plasma aldosterone level in spite of increased plasma angiotensin II following long-term felodipine treatment.     

The contact phase of blood coagulation and renin activation in essential hypertension before and after captopril

The contact phase of blood coagulation in a group of patientssuffering from essential hypertension was studied before andafter captopril administration. The baseline levels of factorXII, factor XI and plasminogen were significantly higher thanin normals and correlated with baseline diastolic blood pressurelevels. On the contrary, plasma prekallikrein was not significantlydifferent from normal. These results suggest the presence ofa hypercoagulable state in essential hypertension. After captopriladministration, factor XII, factor XI and prekallikrein rapidlydecreased, perhaps as a consequence of the drug's effect onthe vascular endothelial surface. There was no correlation betweenthe changes of active and inactive renin and the changes ofprekallikrein and plasminogen levels. Our data do not supportthe view that factor XII-plasma kallikrein or plasmin dependentpathways are involved in the activation of inactive renin invivo. Captopril, by provoking rapid pressure changes, appearsto be able to affect the clotting system.     

Cardiovascular Responsiveness After Isotonic Exercise in Cirrhotic Patients: Study on Sympathoadrenergic and Renin-angiotensin Systems

Objectives: The aim of this study was to evaluate cardiovascular responsiveness after isotonic exercise in cirrhotic patients. Methods: Included were 11 cirrhotic patients and 10 age-matched normal suhjects, who served as controls. Hemodynamic data were obtained on each subject before and after muscle exercise on a treadmill (7 metabolic units). Plasma noradrenaline concentration and plasma renin activity also were determined. Results: In both groups, isotonic exercise increased heart rate and systolic arterial pressure, whereas diastolic arterial pressure was not modified. The increase in heart rate and systolic arterial pressure did not differ significantly between the two groups. Plasma noradrenaline concentration and plasma renin activity also were increased. The changes in plasma noradrenaline concentration and plasma renin activity was higher in cirrbotic patients than in controls ( P < 0.05, P < 0.05), although the differences were not significant when calculated as a percentage. Conclusions: Cardiovascular responsiveness to isotonic exercise is almost intact in cirrhotic patients. However, supernormal activation of the sympathoadrenergic and renin-angiotensin systems is required to maintain cardiovascular homeostasis in these patients.     

Biological Significance of Active and Inactive Renin in Hypertensive Patients

The significance of active and inactive renin was investigated by comparison of an in vitro assay of active, total and inactive plasma renin concentration (APRC, TPRC, IPRC) and plasma angiotensin II concentration (PA II) with an in vivo change in mean arterial pressure (MAP) produced by angiotensin antagonism with saralasin and by angiotensin converting enzyme blockade with captopril. A significant relationship between the changes in MAP during saralasin and captopril with the pre-treatment level of APRC, TPRC and PA II were found; while the pre-existing level of inactive renin was not a predictor for the hypotensive effect of saralasin and captopril. During captopril and saralasin significant increases in TPRC and APRC were found and no change in IPRC.     

Effects of dopamine infusion on the release of atrial natriuretic factor

We evaluated the effects of dopamine infusion (1.5 micrograms/Kg/min for 60 min) on secretion of atrial natriuretic factor before raised diuresis could affect extracellular fluid volume and hence peptide release. We investigated ten healthy subjects without cardiovascular, renal or endocrine disease and ten patients with congestive heart failure (New York Heart Association Classes III and IV). The study protocol required four 30 minute clearance periods: 1st basal, 2nd during placebo, 3rd and 4th during dopamine infusion. We measured diuresis, natriuresis, glomerular filtration rate, blood pressure, heart rate, central venous pressure and plasma concentrations of atrial natriuretic factor, noradrenaline, renin activity, aldosterone and antidiuretic hormone. Blood samples were drawn at the midpoint of each clearance period after measuring blood pressure, heart rate and central venous pressure. Atrial natriuretic factor was determined by radioimmunoassay after chromatographic extraction, noradrenaline was measured fluorometrically while plasma renin activity, aldosterone and antidiuretic hormone concentrations were obtained by radioimmunoassay. During dopamine infusion plasma atrial natriuretic factor plasma levels were significantly raised in healthy subjects while high basal values of the peptide in patients with congestive heart failure were significantly reduced; this trend was also evident for noradrenaline levels in both groups. Plasma renin activity, aldosterone and antidiuretic hormone values remained unchanged in healthy subjects, but plasma renin activity and aldosterone levels dropped significantly in congestive heart failure patients. Diuresis, natriuresis and glomerular filtration rate were significantly increased while blood pressure, heart rate and central venous pressure remained unchanged in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma renin activity in phaeochromocytoma: effects of beta-blockade and converting enzyme inhibition

We measured plasma renin activity and plasma catecholamines in 26 untreated patients with phaeochromocytoma, 18 untreated patients with primary hypertension, and 10 normal control volunteers. Plasma renin activity measured in patients in the supine position, standing position and after walking for 1 h was higher in the subjects with phaeochromocytoma than in those with primary hypertension or in the volunteers (F = 9, P less than 0.001). In all three situations, renin activity was closely correlated with noradrenaline levels in the phaeochromocytoma patients (r = 0.545, r = 0.600, and r = 0.739; P less than 0.01) but not in the subjects with primary hypertension or in the volunteers. The cardioselective beta-blocker acebutolol reduced heart rate, mean blood pressure and renin activity by averages of 20, 12 and 89% respectively in the seven phaeochromocytoma patients given the drug. Captopril decreased mean blood pressure by 19% and raised renin activity by 293% in the nine phaeochromocytoma patients tested. These findings show that in phaeochromocytoma, hypertension is accompanied by high renin levels and that renin release is stimulated in response to noradrenaline overflow. The hypotension observed in response to beta-blockade and captopril provides indirect support for the possibility that renin-dependent mechanisms are involved in the hypertension of phaeochromocytoma.     

Trypsin Activable Renin in Rat Plasma. Effects of Acute and Chronic Perturbation of the Renin System

Plasma levels of active and inactive renin were measured in the rat following manipulation of renin release. in the anesthetized rat intravenous captopril or sodium nitroprusside resulted in elevation of active renin only. Neither active nor inactive renin were altered following ether anesthesia of 2 hour bilaterally nephrectomized animals. Elevated levels of active and total renin were observed in anesthetized Wistar rats that had received oral captopril for a 6 week period. Renin substrate was decreased suggesting that blood angiotensin II exerts a tonic influence on renin substrate. in sodium deplete SHR, sacrificed by decapitation, chronic captopril resulted in a significant increase of both the active and inactive form of the enzyme concomitant with blood pressure reduction. The present data further confirm the independent control of active and inactive renin in the rat.     

Captopril modifies the hemodynamic and neuroendocrine responses to sodium nitroprusside in hypertensive patients

To determine if clinically effective doses of the antihypertensive agent captopril affected the neuronal release of norepinephrine or baroreflex sensitivity, changes in plasma norepinephrine concentration and heart rate were related to the changes in mean arterial pressure seen during the intravenous infusion of stepwise incremental doses of sodium nitroprusside before and during captopril treatment in eight hypertensive men with normal or low plasma renin activity. At all times, significant linear correlations were found between the decrease in mean arterial pressure and the dose of sodium nitroprusside, the increase in heart rate and the decrease in mean arterial pressure, and the increase in plasma norepinephrine concentration and the decrease in mean arterial pressure. When the subjects were treated with captopril (25 mg t.i.d.) for 2 to 4 weeks, supine mean arterial pressure decreased from 130 to 114 mm Hg (-12%; p less than 0.05), heart rate did not change, supine and upright plasma renin activity increased, while supine plasma norepinephrine and epinephrine concentration decreased slightly. Therapy with captopril (25 mg t.i.d.) increased baroreflex sensitivity, as assessed by the slope of the regression line relating the increase in heart rate to the decrease in mean arterial pressure, and increased the responsiveness of the sympathetic nervous system, as assessed by the slope of the regression line relating the increase in plasma norepinephrine concentration to the decrease in mean arterial pressure. These increases were accompanied by a decrease in the slope of the regression line relating the decrease in mean arterial pressure to the dose of sodium nitroprusside and thus were associated with a decreased sensitivity to the vasodepressor effects of sodium nitroprusside.(ABSTRACT TRUNCATED AT 250 WORDS)     

Humoral and hemodynamic effects of increasing doses of captopril in patients with essential hypertension

To compare the hemodynamic and humoral effects of increasing doses of captopril, blood pressure, heart rate, plasma renin activity, plasma aldosterone and angiotensin-converting enzyme activity were measured in 10 patients with mild uncomplicated essential hypertension before and after captopril given in an increasing dose of 25, 50 and 100 mg twice a day, with each dose given for 3 days. The maximal decrease in blood pressure, which was predicted both by basal plasma renin activity values and by the hypotensive response to the first dose, was found after the lowest (25 mg) dose; this effect was detectable for 12 hours independently of the dose administered. Similarly, plasma renin activity was already maximally increased and plasma aldosterone maximally decreased at the lowest dose, while angiotensin-converting enzyme activity showed a dose-dependent inhibition. These data suggest that (1) neither the magnitude nor the duration of the hypotensive effect nor the resin-stimulating and aldosterone-inhibiting actions of captopril are enhanced by drug doses above 25 mg (at least up to 100 mg), and (2) there was no apparent correlation between the degree of angiotensin-converting enzyme inhibition with increasing doses of captopril and the hypotensive effects of the drug.     

The contributions of sympathetic tone and the renin-angiotensin system to severe chronic congestive heart failure: Response to specific inhibitors (prazosin and captopril)

The contribution of sympathetic tone and the renin-angiotensin system to the pathogenesis of chronic heart failure was evaluated. In 20 paired studies of the same 10 patients, the baseline hemodynamic and humoral correlates of congestive heart failure, and the response to alpha adrenergic blockade (prazosin) and angiotensin converting enzyme inhibition (captopril) were assessed. Despite the extent of failure, baseline plasma renin activity ranged from normal to very high. In contrast, baseline plasma catecholamlne levels were always elevated. Baseline plasma norepinephrine reflected the severity of heart failure, correlating inversely with baseline cardiac index before administration of both drugs. Comparable improvement in left ventricular function was noted after acute therapy. Baseline renin and norepinephrine did not predict the response to prazosin, but baseline renin did predict the response to captopril: pulmonary wedge pressure (r = ?0.776, p < 0.01), stroke index (r = 0.752, p < 0.02), systemic vascular resistance (r = ?0.673, p < 0.05).In summary, elevated levels of plasma norepinephrine were inversely correlated with baseline cardiac function, but norepinephrine levels did not change despite improved hemodynamics with specific prazosin therapy. The renin-angiotensin system exhibited a wide spectrum of activity and hemodynamic improvement with captopril was related to this activity. Absence of a correlation between plasma norepinephrine and plasma renin activity suggested that their contributions to vasoconstriction were not interdependent. Increased sympathetic tone was consistent in severe heart failure, whereas renin-angiotensin activity differed widely. The response to captopril can be used to identify a subset of patients with severe heart failure and adverse angiotensin-mediated vasoconstriction.     

Neural and humoral mechanisms involved in blood pressure variability

In order to study blood pressure variability we have measured blood pressure, heart rate, plasma noradrenaline and adrenaline concentration and plasma renin activity during sleep and during the waking process in 20 subjects with borderline hypertension. The responses to a number of standardized tests were also measured. These were reading, mental arithmetic, change in posture, physical exercise and the response to intravenously injected phenylephrine and noradrenaline. The sensitivity of the baroreflex for heart rate control was also determined from the relationship between heart period (R-R interval) and change in systolic pressure after the injection of phenylephrine. Blood pressure was also recorded continuously for 24 hours. From the lowest levels achieved during sleep, blood pressure rose as the subjects regained consciousness but was not restored to its baseline value until mental activity was also restored by reading. Blood pressure rose further with mental arithmetic. These changes were accompanied by a greater proportional rise in plasma adrenaline than in plasma noradrenaline concentrations. Plasma renin activity changed little. The pressor responses to phenylephrine and noradrenaline were inversely related to baroreceptor sensitivity. The fall in blood pressure with sleep and the rise with mental arithmetic was also inversely related to the sensitivity of the reflex. Systolic pressure recorded throughout the day was inversely related to the R-R interval in each subject. The slope of this relationship and range of R-R interval was greatest in the subjects with the most sensitive baroreflexes.     

Captopril in the management of hypertension with renal artery stenosis: Its long-term effect as a predictor of surgical outcome

Fifteen patients with hypertension and unilateral renal artery disease were treated with captopril alone; 10 came to operation and were later assessed postoperatively with no drug treatment. Captopril caused both immediate and sustained decreases in plasma angiotensin II and aldosterone, with increases in plasma active renin and blood angiotensin I concentrations. Decrements in systolic and diastolic pressure 2 hours after the first dose of captopril were closely correlated with the initial decreases in plasma angiotensin II. Blood pressure was decreased by long-term captopril therapy irrespective of whether plasma angiotensin II was abnormally high before treatment. The long-term response of both systolic and diastolic pressure correlated well with the response to surgery. By contrast, the blood pressure decrease 2 hours after the initial dose of captopril variously underestimated and overestimated the decrease during prolonged use of the drug and did not relate to surgical outcome. In patients who, before treatment, had secondary aldosteronism, hyponatremia, hypokalemia and sodium and potassium deficiency, captopril corrected these abnormalities. In the remaining patients, long-term captopril therapy did not alter exchangeable sodium, plasma sodium or total body potassium, although plasma potassium levels increased.