Oral Dose Of Captopril Research Articles

Optimization of chitosan, sodium carboxy methyl celulose and magnesium stearat as mucoadhesive system in captopril tablet

Captopril is an angiotensin-converting enzyme inhibitor (ACE inhibitor) used for the treatment of hypertension and some types of congestive heart failure. It has been reported that the duration of antihypertensive action after a single oral dose of captopril is only 6–8 h. Captopril is most stable at acidic condition and as the pH increases, it becomes unstable and undergoes a degradation reaction. These indicates a promising potential of the captopril mucoadhesive system as an alternative to the conventional dosage form. The objective of the current study was to find an optimum formula of mucoadhesive tablet for captopril using factorial design. Tablets were evaluated for mucoadhesive strength and drug release profile. The studies were perfomed to establish composition of chitosan, sodium CMC and Mg stearat. Such composition could produce mucoadhesive strength with a zero order release kinetics. A 23 factorial design has been applied to systematically optimize the formula. The amounts of chitosan (XA), sodium CMC (XB), and Mg stearat (XC) were selected as independent variables. Mucoadhesive strength and dissolution efficiency (DE480) were selected as dependent variables. According the contour plot suggested that optimum formula will be reach mucoadhesive strength (26-30 g) and DE480 (≥70 %) chitosan at low to middle level (20-35 mg), sodium CMC at middle to high level (150-200 mg), and Mg stearat at low to middle level (4-6 mg). Key words : mucoadhesive, factorial design, DE480 , chitosan, CMC Na, Mg stearat, contour plot

Pharmacological Demonstration of the Additive Effects of Angiotensin-Converting Enzyme Inhibition and Angiotensin II Antagonism in Sodium Depleted Healthy Subjects

A blockade of the hemodynamic and tissue effects of angiotensin II (Ang II) more complete than that presently achieved with usual daily doses of angiotensin converting enzyme (ACE) inhibitors or type 1 Ang II receptor antagonists has potential advantages and risks. Therefore, it is worthwhile to investigate the biological and the hemodynamic effects of the simultaneous blockade of the renin-angiotensin system (RAS) at the two sites where it can be currently achieved, ACE and type 1 Ang II receptors. To investigate this issue, 2 double-blind randomized crossover studies were performed in a model of mild sodium depletion in normotensive volunteers. They ingested single oral doses of captopril 50 mg, losartan 50 mg, their combination or matched placebos, and in a second study, single oral doses of enalapril 10 mg, enalapril 20 mg and the combination of losartan 50 mg with enalapril 10 mg. The combination captopril 50 mg and losartan 50 mg had additive effects on blood pressure fall and renin release in sodium-depleted normotensive subjects. When compared to enalapril 10 mg and the doubling of its dose, the combination of losartan 50 mg and enalapril 10 mg significantly increased both the area under the time curve of mean blood pressure fall and plasma active renin levels. It did not further decrease plasma aldosterone levels. The conclusion is that a more complete blockade of the RAS can be achieved by concomitant administration of an type 1 Ang 11 receptor antagonist and an ACE inhibitor.

A Double-Blind, Parallel, Comparative Evaluation of Amlodipine vs. Captopril in the Monotherapeutic Treatment of Mild and Moderate Essential Hypertension

A double-blind, parallel, comparative study of the antihypertensive efficacy and safety of once-daily oral doses of amlodipine (5-10 mg/day) vs. twice-daily oral doses of captopril (25-50 mg twice daily) in adult patients with mild or moderate essential hypertension (supine diastolic blood pressure of 95-115 mm Hg) was undertaken in two hospital centers. Interim analysis of data from 40 patients shows that amlodipine and captopril both significantly (p < 0.05) reduced blood pressure compared with baseline. Nineteen of 21 (90.5%) amlodipine-treated patients and 15 of 19 (78.9%) captopril-treated patients had their diastolic blood pressure "normalized" (< 90 mm Hg) with mean final doses of 8.2 and 76.7 mg/day, respectively. At the final visit, there were no statistically significant differences between the two treatment groups in either mean supine or standing blood pressure. Minor nonsignificant changes in standing heart rate were observed in both treatment groups. Seven of the 21 amlodipine-treated patients and 3 of the 19 captopril-treated patients reported adverse experiences. No patients in either treatment group discontinued due to adverse events; one patient in the amlodipine group required a dose reduction. These interim data indicate that the overall efficacy and safety profiles of these two drugs are comparable.

The Acute Effect of Captopril on Cerebral Blood Flow, Its CO2 Reactivity, and Cerebral Oxygen Metabolism in Human Volunteers

The present study was undertaken to examine the effect of captopril on cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2) and CO2 reactivity in eight young healthy volunteers. The mean arterial blood pressure (MABP) was measured intraarterially, and CBF was measured by inhaled xenon-1233. The CO2 reactivity was defined as the relative change in CBF per 0.1 kPa change in arterial CO2. During the CO2 reactivity tests, the CBF changes were estimated by the arteriovenous-oxygen-difference method (CBFsat). Median CBF was 52 ml/100 g/min (50-56) and without any significant regional side-to-side asymmetries. No significant change was observed after captopril. The median resting MABP was 90 mm Hg (89-93), and was slightly reduced by 5 mm Hg (4-6) 1 h after an oral dose of captopril (50 mg). CMRO2 was 3.7 ml/100 g/min (3.5-3.8) and was unchanged after captopril. For the entire range of PaCO2 the median slope of the ln(CBFsat) versus PaCO2 regression line was 1.4 (1.3-1.6) at baseline compared to 1.4 (1.3-1.7) after captopril (p = 0.23). Considering the PaCO2 values between 4.0 and 6.5, the CO2 reactivity was 2.4%/0.1 kPa (2.1-2.4) at baseline and increased significantly to 2.9%/0.1 kPa (2.1-3.2) after captopril (p less than 0.05). No side effects were observed. The present study shows an overall unchanged CO2 reactivity; however, with an increased CO2 reactivity of the cerebral vessels for small changes in PaCO2 around the resting value of PaCO2 and a maintained coupling of CBF and CMRO2 after peroral captopril.

Intrapatient comparison of acute hemodynamic, hormonal, and natriuretic responses to captopril versus enalapril in liver cirrhosis

We compared acute hemodynamic, hormonal, and natriuretic responses to a single oral dose of captopril (50 mg) versus enalapril maleate (10 mg) administered to eight patients with biopsy-proved liver cirrhosis. Although the two angiotensin-converting enzyme (ACE) inhibitors lowered (p less than 0.05) blood pressure with no change in heart rate during the early postdose period, captopril produced a greater (p less than 0.05) hypotensive effect than did enalapril. Enalapril caused a greater (p less than 0.01 to 0.05) ACE inhibition than did captopril during the 2- to 48-hour postdose period. Plasma renin activity increased (p less than 0.05) with the two drugs and returned toward baseline by 12 hours after administration. Plasma aldosterone levels, elevated before drug administration, were decreased by the two drugs in a stepwise fashion, but the suppressive effect was greater (p less than 0.01 or p less than 0.05) after captopril than after enalapril. Natriuresis was greater (p less than 0.05) during the first 24-hour period after enalapril than after captopril. The findings indicate that the acute pharmacodynamic responses to the two ACE inhibitors differ in patients with liver cirrhosis. However, the mechanism(s) of the divergent effects of the two drugs and the clinical implications remain obscure from this single-dose study.

Cough Associated with Angiotensin Converting Enzyme Inhibition

The therapeutic inhibition of angiotensin converting enzyme (ACE) is associated with the production of a dry cough, which occurs more commonly in women than men and appears to be unrelated to concurrent illness. At present the exact incidence of ACE inhibitor cough and the substrate of ACE responsible for this effect is unknown. Cough challenge by inhalation of aerosols of tussive agents such as citric acid and capsaicin may be used to study the effect of drug administration on the cough reflex. In normal subjects, an oral dose of captopril (25 mg) causes a significant shift in the dose-response curve to capsaicin inhalation, but not that to distilled water or citric acid. The exacerbation of artificially induced cough by ACE inhibition may be the result of a local increase in perineuronal substance P or bradykinin concentrations within the lung.

Single-Dose Captopril Scintigraphy in the Diagnosis of Renovascular Hypertension

Renal scintigraphy with [99mTc]diethylenetriaminepentaacetic acid (DTPA) and/or sodium-iodine-131-o-iodohippurate (HIP) was performed before and after an oral dose of captopril (50 mg) in 18 patients with renovascular hypertension (RVH) due to renal artery stenosis (RAS) and 18 controls. In every patient with RVH, captopril induced, enhanced or sustained abnormal findings on HIP scintigraphy depending on the degree of RAS. With DTPA scintigraphy, renal function decreased after captopril in ten kidneys with RVH-related RAS and adequate baseline renal function, but this phenomenon was not evident in 11 kidneys with RVH and poor renal function. Captopril did not influence HIP or DTPA studies of kidneys with patent renal arteries (patients after successful renal angioplasty, patients with essential hypertension, contralateral kidneys of patients with unilateral RVH) or ipsilateral kidneys with mild and subcritical (less than 60%) RAS in patients without hypertension and/or normal renal vein renin activity. When HIP and DTPA scintigraphy were compared in the same patients, HIP demonstrated greater sensitivity and specificity than DTPA, particularly in patients with poor renal function. HIP scintigraphy before and after a single dose of captopril may provide a rapid sensitive and minimally invasive test for screening patients with hypertension.

Role of renal kallikrein in modulating the antihypertensive effect of a single oral dose of captopril in normal- and low-renin essential hypertensives.

The antihypertensive efficacy of angiotensin converting enzyme (ACE) inhibitors may result from the blockade of angiotensin II formation but also, theoretically, from the inhibition of kinin breakdown. To test whether a blunted activity of the kallikrein-kinin system might account for the failure of ACE inhibitors in lowering blood pressure (BP) in patients in whom the renin-angiotensin system (RAS) is not enhanced, 31 essential hypertensives with normal or low plasma renin activity (PRA) were evaluated before and after a single oral dose (50 mg) of captopril. A significant fall, in both systolic and diastolic BP, was obtained in the subgroup of patients who were classified as 'normal-kallikrein hypertensives' according to whether their pretreatment urinary kallikrein excretion was within the normal range, while no significant change in BP was observed in 'low-kallikrein hypertensives'. Furthermore, the mean percentage fall in mean BP, throughout the 2 h following captopril administration, was significantly related to the basal value of urinary kallikrein excretion (r = 0.47, P less than 0.05) in all the patients. Our results suggest that blunted activity of the kallikrein system might be responsible for failure of captopril to lower BP in some hypertensive patients.

Urinary kallikrein excretion can predict the blood pressure response to a single oral dose of captopril.

The antihypertensive efficacy of ACE inhibitors depends in theory from the blockade of the angiotensin II formation but also from the inhibition of kinin breakdown. To test whether a blunted activity of the kallikrein-kinin system might account for the failure of ACE inhibitors in lowering BP in patients in whom the renin-angiotensin system is not enhanced, thirty-one essential hypertensives with normal or low PRA were evaluated before and after a single oral dose (50 mg) of captopril. A significant fall both in systolic and diastolic blood pressure (BP) was obtained in the subgroup of patients who were classified as "normal kallikrein hypertensives" according to whether their pretreatment urinary kallikrein excretion was within the normal range, while no significant change in BP was observed in "low kallikrein hypertensives". Furthermore the mean percentage fall in mean BP, throughout the 2 hours following captopril administration, was significantly related to the basal value of urinary kallikrein excretion (r = 0.47, p less than 0.05) in the entire group of patients. Our results suggest that a blunted activity of the kallikrein system might be responsible for failure of captopril in lowering BP in patients in whom the renin-angiotensin system is not pathogenetically implicated.

Effects of captopril on cardiorenal hemodynamics in patients with severe chronic congestive heart failure.

The effects of captopril on cardiorenal function were studied in patients with chronic congestive heart failure. A single oral dose of captopril in 16 patients significantly increased cardiac indices and decreased total systemic vascular resistance. These changes were greater in subjects with higher baseline plasma renin activity (PRA). The increase in PRA and decrease in plasma aldosterone were also greater in this group. During 7 days of captopril therapy, renal plasma flow distinctly increased in 10 patients in whom renal function was followed. The increase in renal blood flow was greater in subjects with higher PRA. Simultaneous infusion of aprotinin in eight of these subjects did not affect the captopril-induced increase in renal plasma flow: these responses were the same in both PRA subgroups. The results suggest that captopril reduces total systemic vascular resistance in patients with chronic congestive heart failure through the inhibition of the renin-angiotensin system and the preferential renal vasodilating effect of captopril seems exclusively to be the sole result of this inhibition, with the kallikrein-kinin system or kinin-mediated prostaglandins not playing a major role.

Maligant hypertension: The Brazilian experience

A 41-year-old white woman was evaluated at Hospital Sao Paulo, Brazil, for hypertension that had been treated inadequately for 6 years. She reported pallor, weakness, scotomata, progressive weight loss, and morning occipital headaches. Three days before admission, she experienced dizziness, blurred vision, intermittent hematuria, shortness of breath, and orthopnea. The day before admission, she had hemoptysis and increased shortness of breath. On physical examination, the patient appeared severely ill; she was pale and dyspneic, and she had jugular venous engorgement. The blood pressure was 250/170 mm Hg; pulse rate, 146 beats/mm; and respirations, 36/mm. Funduscopy revealed increased central light reflex of arteries, arteriovenous nicking, arterial vasospasm, cotton-wool and hemorrhagic patches, and bilateral papilledema. Rales were detected in the lower two-thirds of both lung fields. Tachycardia and a gallop rhythm without cardiac murmurs also were present. There was epigastric tenderness and the liver was enlarged and tender. All peripheral pulses were present and symmetrical, and there were no bruits. No edema was present, but muscular wasting of the extremities was apparent. The electrocardiogram revealed left ventricular hypertrophy and sinus tachycardia. A plain chest x-ray film revealed an increased cardiac silhouette and left ventricular enlargement; the pulmonary circulation was congested. Laboratory tests revealed the following: blood pH, 7.41; P02, 53 mm Hg; PCO2, 31 mm Hg; BUN, 83 mg/dI; creatinine, 6.5 mg/dl: serum sodium, 130 mEq/liter; serum potassium, 4.7 mEq/liter. Urinalysis revealed 1.5 g/liter of protein with many white blood cells and red blood cells; hemoglobin, Il g/dl; hematocrit, 33%; white blood cell count, 11,900/mm3 with 82% total neutrophils; platelets, 250,000/mm3; sedimentation rate, 45 mm/hr. The serum CPK was normal; the serum LDH was elevated (595 U), as was the amylase (565 U). The peripheral plasma renin activity was 10 ng/ml/hr. Following admission the blood pressure was reduced to 160/100 mm Hg by the intravenous administration of diuretics and sodium nitroprusside. The pulse rate diminished to 100 beats/mm. and dyspnea disappeared. On the following day, the nitroprusside infusion was discontinued for 4 hours, but the blood pressure again rose to 250/170 mm Hg. The patient was given 150mg of captopril orally, and hemodynamic changes were measured via a Swan-Ganz catheter. Two hours after captopril was given, mean arterial pressure decreased from 175 to 140 mm Hg. and the pulmonary wedge pressure decreased from 5.5 to 3.0 mm Hg. The cardiac index increased from 3.6 to 4.! liter/m2; no change was observed in the heart rate. In spite of continued oral administration of 50 mg of captopril every 6 hours and 40 mg of furosemide every 12 hours, the blood pressure again soared to the level present on admission. Two days after the first dose of captopril. another single oral dose of captopril, 50 mg, was administered when the blood pressure was 250/140 mm Hg. Neither the arterial pressure nor any other hemodynamic parameters changed significantly following this dose. By this time the BUN and plasma creatinine had risen to 104 mg/dl and 9.7 mg/dl, respectively. After the lack of response to captopril, 1700 ml of fluid was withdrawn by ultrafiltration over 4 hours. Striking decreases in blood pressure, central venous pressure, and cardiac index were observed, and administration of normal saline and packed red cells was necessary to restore intravascular volume. intravenous nitroprusside therapy again controlled blood pressure. The following day administration of only alpha-methyldopa (1 g/day) and furosemide (80 mg/day) kept the blood pressure under control, and the nitroprusside infusion was discontinued. Two days after this oral regimen was instituted (3 days after admission), the blood pressure again rose, and hemodialysis was begun because of further deterioration of renal function. Several therapeutic maneuvers, including the use of minoxidil and beta blockers, were tried without achieving successful control of the hyperten ', and the patient died from sepsis 9 months later while still in a chro hemodialysis program.

Effect of DOCA-salt on Angiotensin Dependency and Surgical Reversal of Hypertension in Two-kidney, One Clip Renal Hypertensive Rats

The development of hypertension in two-kidney, one clip renal hypertensive rats (2K, 1C RHR) was not altered by treatment with DOCA and saline solution as drinking fluid for two months of observation. However, the administration of DOCA and salt suppressed plasma renin activity (PRA), the renal renin content (RRC) of the clipped kidney and the response to a single oral dose of captopril (10 mg/kg). The weight of the contralateral kidney was increased by the administration of DOCA-salt, while that of the ischaemic kidney was not changed. The withdrawal of DOCA-salt treatment restored the PRA and the effects of captopril to a similar degree to the non-treated group. The acute hypotensive effects of captopril were reduced on the 10th week compared with the 7th week after renal arterial constriction in 2K, 1C RHR. The fall in blood pressure induced by captopril significantly correlated with the initial PRA both in the 7th and 10th week after clipping. There was a significant correlation between PRA and RRC of the clipped kidney. Rats previously treated with DOC-salt had either removal of the contralateral kidney with removal of the clip from the ischaemic kidney, or removal of the ischaemic kidney. Blood pressure fell to normal levels in the unclipped group and in the nephrectomy group, but the fall in the latter group was transient and within two weeks had risen to significantly higher levels than in the unclipped group. It is concluded that structural vascular change following DOC-salt hypertension is insufficient to cause persisting hypertension except when it occurs in the renal circulation.

Tissue distribution of captopril, reducible captopril conjugates and S-methylcaptopril in the rat

The tissue distribution of captopril, an antihypertensive drug possessing a free sulfhydryl group, and its sulfur-conjugated metabolites was studied in rats by gas chromatography-mass spectrometry at 15, 30 and 60 min following a single 10 mg/kg oral dose of captopril. It was found that tissue accumulation of captopril was rapid with both free and oxidized-forms already present at 15 min post-dose. A maximum concentration of captopril was achieved at 30 min in tissues studied, being substantially higher in kidney (14.2 μg/g), with lesser amounts occurring in liver, lung, heart, blood cells, spleen and plasma in that order. Oxidized disulfide forms of captopril were usually present in the same or slightly higher proportion than free captopril except for liver which only contained detectable disulfides at 15 min after oral dosing. S-methylcaptopril was also present at 30 min in all tissues examined with highest levels occurring in liver and kidney (1.05 μg/g) followed by plasma, lung, heart, spleen and blood cells.

What stimulates the renin-angiotensin system in rats with two-kidney renal hypertension?

1. Blood pressure, the hypotensive effect of captopril, plasma renin activity, renal renin content and kidney weight were measured in the two-kidney—one-clip model, the one-kidney—one-clip model and the two-kidney—one-clip model with the ureter of the contralateral kidney ligated in rats. The ureteric ligation was performed to abolish urinary excretion from the contralateral kidney in the two-kidney—one-clip model. 2. The development of hypertension after renal artery constriction was earlier and greater in the one-kidney—one-clip model and the two-kidney—one-clip model with ureter of the contralateral kidney ligated than in the two-kidney—one-clip model. A single oral dose of captopril produced a greater fall in blood pressure in both the two-kidney models than in the one-kidney—one-clip group. 3. Plasma renin activity and renal renin content of the clipped kidney were higher in the two-kidney model rats, whether or not the ureter had been ligated, than in the one-kidney—one-clip model animals, although more than half the rats from the two-kidney model had normal values. There was a significant correlation between plasma renin activity and the response to captopril in all groups, whereas in none of the three groups was the correlation between plasma renin activity and blood pressure significant. 4. The clipped kidney had a higher renin content than did the contralateral kidney, and the weight of the ischaemic kidney was decreased compared with the contralateral kidney whether it was untouched or had its ureter ligated. The weight of the clipped kidney was in the order one-kidney—one-clip model &amp;gt; two-kidney—one-clip model with ureter of the contralateral kidney ligated &amp;gt; two-kidney—one-clip model. 5. It was concluded that the renin-angiotensin system was stimulated to the similar degree in some animals for the two-kidney—one-clip models, whether or not the ureter of the contralateral kidney had been ligated, compared with the one-kidney—one-clip animals. This finding suggests that the contralateral kidney can stimulate renin secretion and synthesis in the clipped kidney independently of Na+ excretion.

Renin-angiotensin system inhibition in acute myocardial infarction in dogs. Effects on systemic hemodynamics, myocardial blood flow, segmental myocardial function and infarct size.

Acute left anterior descending coronary artery occlusion was produced in 21 conscious, chronically instrumented dogs. Forty minutes after coronary occlusion, nine dogs were given i.v. teprotide, 25 micrograms/kg/min, followed by oral doses of captopril, 10 mg/kg every 8 hours for 24 hours. The remaining 12 dogs served as saline-infused controls. In all dogs, acute coronary occlusion increased plasma renin activity and peripheral vascular resistance and reduced cardiac output, but did not change mean aortic blood pressure significantly. Teprotide significantly (p less than 0.05) decreased peripheral vascular resistance (from 3804 +/- 1158 to 2876 +/- 816 dy-sec-cm-5) (+/- SD) and mean aortic pressure (from 117 +/- 12 to 107 +/- 15 mm Hg), and increased cardiac output (from 2.63 +/- 0.67 to 3.12 +/- 0.74 l/min). Teprotide also produced a relative increase in flow to the renal and splanchnic circulations compared with the saline-treated controls. There were, however, no differences in segmental systolic shortening, blood flow in the normal or ischemic myocardium, or infarct size. These results indicate that the renin-angiotensin system may play an important role in dogs with acute coronary occlusion and that blockade of this system lowers systemic blood pressure and improves cardiac output. However, direct effects of renin-angiotensin system blockade on the myocardium are lacking; there were no changes in myocardial blood flow, myocardial mechanics or infarct size.

Effects of the converting enzyme inhibitor captopril on blood coagulation and fibrinolysis in man.

Systematic blood coagulation analyses were conducted in 32 severely hypertensive patients treated with the angiotensin converting enzyme inhibitor captopril. Two hours after the first captopril dose, fibrin monomer complexes had already increased. This rise was even more distinct after 26 h and 1 week. Tests after 6 and 12 months of therapy showed a regression of fibrin monomer complexes to pretreatment values. In several patients with a marked increase in fibrin monomer complexes, the partial thromboplastin time (PTT) became shorter and antiplasmin activity increased. The most pronounced increase in fibrin monomer complexes was seen in patients with a rapid and excessive blood pressure reduction. The concentration of fibrin monomer complexes also rose in 15 healthy normotensive subjects, after a single oral dose of captopril (25 mg). Additionally, the PTT was shortened and antiplasmin significantly rose. An inhibition of fibrinolysis by captopril could be demonstrated by the effect on fibrin plates and thrombus weight after streptokinase. Out of 58 patients with severe hypertension and atherosclerosis treated with captopril, 7 patients suffered vascular complications during antihypertensive therapy: myocardial infarction (n = 2), coronary insufficiency (1), cerebral ischemia (1), renal insufficiency (3). These ischemic lesions may be partly explained by the alterations of coagulation and fibrinolysis under captopril therapy.

Acute effects of captopril on blood pressure and circulating hormone levels in salt-replete and depleted normal subjects and essential hypertensive patients.

1. The acute effects of a single oral dose of captopril on blood pressure, pulse rate and circulating levels of angiotensin I (ANG I), angiotensin II (ANG II), renin, bradykinin and catecholamines were studied in three groups: eight normal subjects, six salt-depleted normal subjects and 16 patients with essential hypertension. 2. Captopril treatment did not cause any significant fall in supine blood pressure in salt-replete normal subjects or patients with untreated essential hypertension but was associated with a fall in mean blood pressure from 85 +/- 2 to 75 +/- 2 mmHg in salt-depleted normal subjects and from 131 +/- 7 to 117 +/- 5 mmHg in patients with essential hypertension treated with diuretics. There was no change in pulse rate in any group. 3. Hormonal responses to captopril were qualitatively similar in the three groups and consisted of significant falls in ANG II with corresponding increases in ANG I and plasma renin concentration. The changes in plasma renin concentration and ANG I were greater in salt-depleted normal subjects (mean values at 90 min were 1140% and 990% of basal levels respectively) than in salt-replete normal subjects (410%, 190%) and were blunted in patients with essential hypertension (140%, 120%). Blood bradykinin, noradrenaline and adrenaline concentrations did not change after captopril in any group. 4. The parallel fall in blood pressure and ANG II levels in salt-depleted normal subjects is consistent with maintenance of blood pressure by increased levels of ANG II in sodium depletion. 5. The failure of captopril to reduce acutely blood pressure in patients with essential hypertension despite suppression of plasma ANG II and without change in circulating bradykinin confirms that the renin-angiotensin system does not play a primary role in essential hypertension.