Captopril in clinical hypertension. Changes in components of renin-angiotensin system and in body composition in relation to fall in blood pressure with a note on measurement of angiotensin II during converting enzyme inhibition.

The effect of the converting enzyme inhibitor captopril on arterial pressure, the components of the renin-angiotensin-aldosterone system, and body sodium and potassium content was studied in eight hypertensive patients with renal artery stenosis and, in conjunction with diuretics, in seven patients with hypertension unresponsive to previous treatment. Two hours after the first dose, captopril caused significant falls in systolic and diastolic pressures, plasma angiotensin II, and aldosterone, with converse increases in angiotensin I and both active and total renin; the initial fall in diastolic pressure was significantly related to the drop in plasma angiotensin II. The biochemical changes were sustained during prolonged treatment, even when diuretics were added. One untreated patient with renal artery occlusion had severe secondary aldosterone excess, was sodium and potassium depleted, and severely hyponatraemic and hypokalaemic; captopril restored blood pressure, plasma electrolyte concentrations, and exchangeable sodium and total body potassium to normal. In one man with renal artery stenosis and overall renal impairment captopril led to sodium retention, and blood pressure did not fall until a diuretic was added. In the remaining patients with renal artery stenosis, pretreatment renin, angio tensin II, and aldosterone concentrations were either normal or only modestly raised, and plasma electrolyte concentrations and body content of sodium and potassium were normal. Captopril alone controlled arterial pressure in all, three cases showing a gradual fall of pressure over the first six weeks of treatment; no significant changes in exchangeable sodium or total body potassium were seen. The group of patients with previously intractable hypertension were all controlled with a combination of captopril and diuretic.     

Effect of angiotensin blockade and converting enzyme inhibition on renovascular hypertension: comparison between unilateral and bilateral renal artery stenosis

The response to angiotensin II analog infusion during sodium deletion and the effects of a one-month captopril treatment were compared between 15 renovascular hypertensive patients with unilateral and 6 with bilateral renal artery stenosis. Plasma renin activity, its response to sodium depletion, and the renal vein renin ratio during sodium depletion were greater in unilateral than in bilateral stenosis. A fall in diastolic blood pressure induced by analog infusion during sodium depletion was correlated with the preinfusion plasma renin activity and with the renal vein renin ratio. Treatment with captopril showed a comparable hypotensive effect in unilateral and bilateral stenosis. The reduction in blood pressure was not correlated with the pretreatment renin levels or changes in blood pressure observed during analog infusion. Plasma renin activity rose and plasma aldosterone level fell in all patients. These results indicate that the mechanism maintaining high blood pressure is more renin dependent in unilateral than in bilateral stenosis and that the long-term effect of captopril does not depend solely on the suppression of the renin-angiotensin-aldosterone system.     

Hemodynamic and hormonal responses during captopril therapy for heart failure: Acute,chronic and withdrawal studies

The hemodynamic and hormonal responses to acute and chronic captopril therapy and to its temporary withdrawal were studied in seven patients with congestive heart failure. Maximal hemodynamic and hormonal effects were reached with 25 to 50 mg doses of captoprit. Since plasma angiotensin II levels were significantly higher $\text{6}\text{1}\text{2}$ hours than 1 hour after administration of captopril, the drug should be given not less often than three times daily. No evidence of hormonal “escape” during long-term ($\text{mean}\text{4}\text{1}\text{2}\text{months}$) captopril therapy was observed, and initial hemodynamic responses were well maintained. Cessation of captopril administration resulted in abrupt increases in circulating angiotensin II levels, in arterial pressure, and in both pulse rate and plasma norepinephrine, but no decrease in cardiac function in the short-term was detected.     

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.     

Twice-daily low-dose captopril in diuretic-treated hypertensives

Twice-daily captopril (25 mg) and placebo were compared in ten hypertensive patients who were already receiving bendrofluazide. After six weeks therapy, captopril produced significant antihypertensive effects one to six hours after dosing but these did not persist at eleven to twelve hours. Plasma renin concentration was increased for twelve hours after captopril but inhibition of angiotensin II activity was lost by twelve hours. During the period when captopril reduced blood pressure significantly, effective renal plasma flow and hepatic blood flow were unchanged although renal vascular resistance was reduced. There was no evidence that captopril altered plasma sodium, potassium or magnesium concentrations following bendrofluazide. Thus, in thiazide-treated patients, captopril 25 mg produces significant blood pressure reduction for at least six hours after dosing, without impairing renal or hepatic blood flow. However, twice-daily low-dose captopril does not adequately control blood pressure throughout the dosage interval.     

Relationships between blood pressure, heart rate and plasma epinephrine, norepinephrine, angiotensin II concentrations, plasma renin activity during chronic guanfacine therapy in patients with essential arterial hypertension

The evolution of blood pressure, heart rate, epinephrine, norepinephrine, angiotensin II and plasma renin activity has been studied in 10 patients with essential arterial hypertension before and during a two months period of treatment with guanfacine, a new centrally acting hypotensive drug. Guanfacine was proven effective in lowering both systolic and diastolic supine and standing blood pressure. A decrease in supine and standing norepinephrine plasma concentrations and plasma renin activity was observed. No change was seen in epinephrine or angiotensin II. The fall in supine blood pressure observed during the treatment period was positively correlated with the change in norepinephrine.     

Acute and chronic systemic and pulmonary hemodynamic effects of angiotensin converting enzyme inhibition with captopril in hypertensive patients

The effects of the angiotensin converting enzyme inhibitor captopril were studied in 14 patients with essential or renovascular hypertension 75 minutes after ingestion of 25 mg of the drug, and after 2 months of therapy with 150 to 600 mg/day. Captopril acutely decreased mean brachial arterial pressure by 16.3 mm Hg (p < 0.001); the decrease was 7.6 mm Hg (p < 0.01) during long-term therapy at the higher dose level. The changes in mean brachial arterial pressure were significantly related to control plasma levels of angiotensin II. The acute hypotensive effect of captopril was based on a 10 percent decrease (p < 0.01) in systemic vascular resistance with essentially unchanged cardiac output and heart rate. Pulmonary capillary wedge pressure decreased by 2.3 mm Hg (p < 0.001) with unchanged pulmonary vascular resistance. During long-term treatment systemic vascular resistance decreased by 29 percent (p < 0.001). Oxygen consumption increased by 15 percent (p < 0.01) with a concomitant 16 percent Increase in cardiac output (p < 0.01), characterized by an increased stroke volume and unchanged heart rate; one patient experienced angina pectoris that may have been related to these hemodynamic changes. The decrease in pulmonary capillary wedge pressure was maintained, and right atrial pressure decreased (?1.4 mm Hg; p < 0.05).The data indicate that the action of captopril is characterized by arteriolar and possibly venous dilatation. The increase in cardiac output during long-term treatment seems to be associated with a hypermetabolic state and in patients with very severe hypertension, with restoration to normal of mildly decreased left ventricular function.     

Antihypertensive effects of captopril and saralasin in essential and renal hypertension

The antihypertensive effect of captopril and its mechanism of action were studied in patients with essential and renal hypertension. In mild essential hypertension (n = 12), during monotherapy with captopril (50 to 450 mg, 4 to 12 weeks) blood pressure was normalized in seven, improved in two and remained unchanged in three patients, plasma levels of active and acid-activatable inactive renin significantly increased and angiotensin II decreased, whereas no consistent changes in urinary kallikrein excretion occurred. In severe renal (n = 14) and essential (n = 9) hypertension, blood pressure was normalized in eight (seven with renal hypertension), improved in seven and unchanged in eight patients, when captopril (50 to 450 mg, 3 to 15 months) was added to the antihypertensive medication. In one patient with stenosis in a transplanted renal artery reversible renal failure occurred during captopril therapy possibly because of a steep initial decrease in blood pressure, although a toxic effect of the drug cannot be excluded. In another series of 12 renal and 8 essential hypertensive patients, a significant correlation between the acute effect of captopril (within 90 minutes) and saralasin on blood pressure was demonstrated (r = 0.71, p < 0.001). The change in blood pressure after either drug was significantly related to the initial plasma renin concentration.In conclusion, captopril sems to be an effective antihypertensive agent in essential and renal hypertension. Renal function should be monitored during captopril therapy. Our studies suggest that captopril decreases blood pressure by inhibiting the vasopressor action of the renin-angiotensin system.     

Acute and chronic effects of the angiotensin-converting enzyme inhibitor captopril in severe hypertension

In this study the acute and chronic effect of the converting enzyme inhibitor captopril was investigated in a relatively large number of patients (acute: n = 78, chronic: n = 67) with various forms of severe hypertension, the majority of cases being resistant to a standardized triple therapy (100 mg of hydrochlorothiazide or 80 to 500 mg of furosemide, 320 mg of propranolol and 200 mg of hydralazine). Up to an observed period of 240 minutes, a single oral dose of 25 mg of captopril led to a significant and marked decrease in systolic and diastolic blood pressure. The acute antihypertensive effect of captopril was more pronounced in patients with renovascular than in those with essential or renal parenchymal hypertension. Similar differences among the three groups of patients were also observed during chronic treatment. Over a period of 18 months, patients with renovascular hypertension showed both a more pronounced decrease in mean diastolic blood pressure values and a significantly higher percentage of cases with excellent blood pressure control (diastolic blood pressure 95 mm Hg or less). Under long-term conditions, about 90 percent of all patients required a diuretic and a substantial percentage also needed propranolol as a third drug. Positive correlations between pretreatment plasma renin activity levels and captopril-induced blood pressure reduction were found under acute conditions only. The most frequent side effects were skin manifestations, taste disturbances, dizziness and unproductive cough. Serious adverse effects were rare and included one case of leukopenia and one of the nephrotic syndrome, both being reversible after withdrawal of captopril.Our results demonstrate that captopril is a very potent blood pressure lowering agent in severe hypertension especially in cases of renovascular hypertension. However, currently the potential risk of serious side effects should induce the physician to reserve this drug for those patients with truly resistant hypertension.     

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.     

Fluctuations in the plasma angiotensin I converting enzyme activity during long-term treatment with captopril

Eight hypertensive patients on chronic captopril treatment were studied: blood pressure, plasma converting enzyme activity (pCEA) and various components of plasma renin-angiotensin-aldosterone system were measured repeatedly, immediately before and up to 7 hours after the usual morning dose of captopril in 5 patients, or a matching placebo in 3 patients. In the patients, receiving a placebo no significant changes were observed over a 7 hour period in pCEA, plasma rénin activity (PRA), plasma angiotensin II (ANG II) plasma aldosterone (PAC) and blood pressure. In patients receive captopril (200 mg) pCEA rapidly decreased, reaching after 2 hours a minimum, corresponding to nearly 20 per cent of its reference value. Thereafter pCEA increased and after 7 hours remained only slightly depressed. Within the first hour after captopril intake a small but significant decrease of ANG II and PAC was observed, while PRA and blood pressure remained unchanged throughout the study period. A continuous low pCEA level is therefore not necessary to achieve a sustained blood pressure lowering effect during chronic captopril treatment.     

Captopril in heart failure. A double blind controlled trial

The effect of the converting enzyme inhibitor captopril as long term treatment was investigated in 14 patients with severe congestive heart failure in a double blind trial. Captopril reduced plasma concentrations of angiotensin II and noradrenaline, with a converse increase in active renin concentration. Effective renal plasma flow increased and renal vascular resistance fell; glomerular filtration rate did not change. Serum urea and creatinine concentrations rose. Both serum and total body potassium contents increased; there were no long term changes in serum concentration or total body content of sodium. Exercise tolerance was appreciably improved, and dyspnoea and fatigue lessened. Left ventricular end systolic and end diastolic dimensions were reduced. There was an appreciable reduction in complex ventricular ectopic rhythms. Adverse effects were few: weight gain and fluid retention were evident in five patients when captopril was introduced and two patients initially experienced mild postural dizziness; rashes in two patients did not recur when the drug was reintroduced at a lower dose; there was a significant reduction in white cell count overall, but the lowest individual white cell count was 4000 X 10(6)/l. Captopril thus seemed to be of considerable value in the long term treatment of severe cardiac failure.     

Captopril in heart failure. A double blind controlled trial.

The effect of the converting enzyme inhibitor captopril as long term treatment was investigated in 14 patients with severe congestive heart failure in a double blind trial. Captopril reduced plasma concentrations of angiotensin II and noradrenaline, with a converse increase in active renin concentration. Effective renal plasma flow increased and renal vascular resistance fell; glomerular filtration rate did not change. Serum urea and creatinine concentrations rose. Both serum and total body potassium contents increased; there were no long term changes in serum concentration or total body content of sodium. Exercise tolerance was appreciably improved, and dyspnoea and fatigue lessened. Left ventricular end systolic and end diastolic dimensions were reduced. There was an appreciable reduction in complex ventricular ectopic rhythms. Adverse effects were few: weight gain and fluid retention were evident in five patients when captopril was introduced and two patients initially experienced mild postural dizziness; rashes in two patients did not recur when the drug was reintroduced at a lower dose; there was a significant reduction in white cell count overall, but the lowest individual white cell count was 4000 X 10(6)/l. Captopril thus seemed to be of considerable value in the long term treatment of severe cardiac failure.     

Prediction of sustained antihypertensive efficacy of chronic captopril therapy: Relationships to immediate blood pressure response and control plasma renin activity

The blood pressure (BP) lowering effect of the orally active angiotensin converting enzyme inhibitor, captopril (SQ 14225), was studied in 59 hypertensive patients maintained on a constant sodium intake. Within 2 hours of the first dose of captopril BP fell from $\text{171}\text{107}$ to a maximum low of $\text{142}\text{92}\text{mm Hg}$ (p < 0.001), and after 4 to 8 days of treatment BP averaged $\text{145}\text{94}\text{mm Hg}$ (p < 0.001). The magnitude of BP drop induced by captopril was significantly correlated to baseline plasma renin activity (PRA) both during the acute phase (r = ?0.38, p < 0.01) and after the 4 to 8-day interval (r = ?0.33, p < 0.01). Because of considerable scatter in individual data, renin profiling was not precisely predictive of the immediate or delayed BP response of separate patients. However, the BP levels achieved following the initial dose of captopril were closely correlated to BP measured after 4 to 8 days of therapy, and appeared to have greater predictive value than control PRA of the long-term efficacy of chronic captopril therapy despite marked BP changes occurring in some patients during the intermediate period. Because of these intermediate BP changes, addition of a diuretic to enhance antihypertensive effectiveness of angiotensin blockade should be restrained for several days after initiation of captopril therapy.     

Efficacy of an angiotensin II receptor antagonist in managing hyperaldosteronism

OBJECTIVE: To determine whether an angiotensin II receptor antagonist decreases blood pressure in patients with hyperaldosteronism and hypertension who are taking other antihypertensive agents. DESIGN: A double-blind randomized placebo-controlled crossover study. PATIENTS AND METHODS: Blood pressure and hormonal responses to 2-week courses of placebo/irbesartan (150 mg/day given by mouth at 08.05 h) were assessed in 10 patients with hyperaldosteronism. Clinic blood pressure was measured by sphygmomanometer, and plasma concentrations of aldosterone, cortisol, angiotensin II, electrolytes and renin activity (PRA) were determined weekly. Automated 24 h ambulatory blood pressure recordings were made at the end of the active and placebo phases. RESULTS: Irbesartan caused a post-dose decrease in ambulatory blood pressure (systolic, P = 0.02; diastolic, P = 0.05) in the period from 10.00 h to 20.00 h. Clinic blood pressure, measured at trough, was not significantly decreased. Plasma aldosterone decreased (P < 0.03) and PRA increased (P < 0.04) in the first week of active treatment with irbesartan, but differences between the placebo and active-treatment groups were not significant in the second week. There were no significant changes in plasma concentrations of angiotensin II, cortisol or potassium in either week. In the second week of irbesartan treatment, there were associations between change in plasma aldosterone and maximal change in ambulatory blood pressure (systolic and diastolic). CONCLUSION: Irbesartan has a role in combination antihypertensive treatment of patients with hyperaldosteronism.     

Captopril in the long-term treatment of essential hypertension: changes in the renin-angiotensin-aldosterone system

We investigated changes in the renin-angiotensin-aldosterone system in seven patients with essential hypertension during treatment with captopril (SQ 14225) (300 to 450 mg/day) for 12 months. While blood pressure decreased, the plasma-renin concentration increased to 700 percent of the initial value (6.1 +/- 2.5 ng angiotensin l/ml . h) and angiotensin I increased to about 300 percent of the basal value (179 +/- 32 pg/ml). Converting enzyme inhibition resulted in a 30 percent decrease in plasma angiotension II levels from a basal level of 66 +/- 21 pg/ml. Plasma aldosterone decreased 52 percent from 63 +/- 13 pg/ml initially. These changes in hormone levels were maintained throughout the study. There was no significant change in serum sodium and serum potassium concentration.     

Haemodynamic and hormonal effects of captopril in primary pulmonary hypertension.

The treatment of primary pulmonary hypertension is unsatisfactory. Since, in animals, experimental pulmonary vasoconstriction may be mediated in part by angiotensin II, we treated five primary pulmonary hypertensive patients with captopril for four days. To ensure accuracy of haemodynamic and hormone data, the patients were studied under conditions of constant body posture, regulated dietary sodium and potassium intake, and unchanged diuretic therapy. Captopril reduced mean pulmonary arterial pressure in parallel with plasma angiotensin II levels. Right ventricular ejection fraction recordings increased considerably in three of four patients. Systemic arterial pressure fell, but there was no change in right atrial pressure, cardiac output, or heart rate. The decline in plasma (and urine) aldosterone levels presumably contributed to the positive cumulative potassium balance and the rise in plasma potassium (mean 0.7 mmol/1). These encouraging results suggest that converting enzyme inhibitors warrant a formal trial with prolonged follow up in the treatment of primary pulmonary hypertension.     

Determinants of the initial effects of captopril on blood pressure, glomerular filtration rate, and natriuresis in mild-to-moderate chronic congestive heart failure secondary to coronary artery disease

Whereas angiotensin-eonverting enzyme inhibitors are now indicated for all grades of chronic heart failure, the 2 adverse effects that limit use of these drugs are systemic hypotension and renal dysfunction. The recognized clinical correlates such as hyponatremia and high diuretic dose, which predict occurrence of these adverse effects in severe chronic congestive heart failure (CHF), are rarely evident in patients with mild-to-moderate CHF. Accordingly, we studied 36 patients with stable, moderate CHF in a double-blind, placebo-controlled, crossover fashion to evaluate by multiple discriminate regression analysis the pathophysiologic determinants of changes in blood pressure, glomerular filtration rate, and urinary sodium excretion after initial converting enzyme inhibition with captopril 25 mg. A captopril-mediated decrease in mean arterial pressure was predicted by 3 factors (r² = 0.74): the decrease in serum angiotensin II (F RATIO = 10.3, p <0.01), the decrease in plasma norepinephrine (F = 8, P = 0.02), and, inversely by pretreatment mean arterial pressure (F = 5.6, P = 0.04), patients with higher initial values exhibiting greater decreases in response to captopril. A captopril-mediated decline in glomerular filtration rate, determined by radioisotope elimination, was also predicted by 3 factors (r² = 0.67): a decrease in renal plasma flow (F = 48.6, p <0.01), low pretreatment glomerular filtration rate (F = 11.1, p <0.01), and low absolute post-treatment serum angiotensin II (F = 5, P = 0.04). Change in urinary sodium excretion was related directly to change in glomerular filtration rate (F = 30.4, p <0.01) and inversely to change in angiotensin II level (F = 4.7, P = 0.05) in response to captopril (r² = 0.73). Captopril-mediated effects on blood pressure did not determine changes in either glomerular filtration rate or urinary sodium excretion.

These findings emphasize the central role for circulating angiotensin II in CHF as the modifiable factor that mediates a potent antinatriuretic action while simultaneously playing a part in maintaining systemic blood pressure and, independently, in maintaining glomerular filtration rate.     

Haemodynamic and hormonal effects of captopril in primary pulmonary hypertension

The treatment of primary pulmonary hypertension is unsatisfactory. Since, in animals, experimental pulmonary vasoconstriction may be mediated in part by angiotensin II, we treated five primary pulmonary hypertensive patients with captopril for four days. To ensure accuracy of haemodynamic and hormone data, the patients were studied under conditions of constant body posture, regulated dietary sodium and potassium intake, and unchanged diuretic therapy. Captopril reduced mean pulmonary arterial pressure in parallel with plasma angiotensin II levels. Right ventricular ejection fraction recordings increased considerably in three of four patients. Systemic arterial pressure fell, but there was no change in right atrial pressure, cardiac output, or heart rate. The decline in plasma (and urine) aldosterone levels presumably contributed to the positive cumulative potassium balance and the rise in plasma potassium (mean 0.7 mmol/1). These encouraging results suggest that converting enzyme inhibitors warrant a formal trial with prolonged follow up in the treatment of primary pulmonary hypertension.     

Angiotensin II levels, hemodynamics, and sympathoadrenal function after low-dose captopril in heart failure

The angiotensin converting enzyme inhibitor captopril improves the altered hemodynamics in many patients with chronic heart failure, but the first dose may precipitate hypotension. Ten patients with chronic heart failure were studied, nine with high plasma concentrations of renin and one with a low concentration. Frequent measurements of plasma concentrations of angiotensin II, renin, and catecholamines were made over 60 minutes after a small dose (6.25 mg) of captopril and related to concurrently measured hemodynamic variables. Captopril caused a decrease in systemic and pulmonary artery pressure and an increase in cardiac index, and these changes coincided with reductions in the plasma concentrations of angiotensin II and increases in plasma concentrations of renin. The hemodynamic changes were accompanied by reductions in the plasma concentrations of norepinephrine but transient increases in plasma concentrations of epinephrine in patients in whom vasomotor syncope developed. The patient with a low plasma renin concentration showed little hemodynamic response to the drug. It is concluded that vasomotor syncope occurs quite frequently in patients with severe chronic heart failure after captopril in a small dose and is associated with a selective increase in epinephrine secretion from the adrenal medulla.