enalapril and Hyperaldosteronism

Topics: Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Captopril; Dipeptides; Drug Eruptions; Drug Interactions; Enalapril; Heart Failure; Humans; Hyperaldosteronism; Hypertension; Hypertension, Renal; Kidney Diseases; Neutropenia; Proline; Taste Disorders

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Captopril; Dipeptides; Enalapril; Heart Failure; Hemodynamics; Humans; Hyperaldosteronism; Hypertension; Kinetics; Oligopeptides; Renin; Teprotide

The study reported here prospectively evaluated the prevention of diuretic-induced secondary hyperaldosteronism and hypokalemia by a converting enzyme inhibitor, enalapril (MK 421). Eighteen normal subjects were randomized into three groups: (1) a HCTZ group (hydrochlorothiazide (HCTZ) 50 mg/day); (2) a MK-421 group (MK-421 10 mg/day); and (3) a HCTZ + MK-421 group [HCTZ 50 mg/day plus MK-421 10 mg/day]. Following a five-day control and a 28-day treatment period, the HCTZ group demonstrated an attenuated but persistent secondary hyperaldosteronism and hypokalemia, the MK-421 group manifested a gradual decline in aldosterone secretion, and the HCTZ + MK-421 group had a delayed but effective correction of secondary hyperaldosteronism and hypokalemia at 28 days but not before. In conclusion, MK-421 reversed diuretic-induced secondary hyperaldosteronism and hypokalemia after 28 days of hydrochlorothiazide therapy. Therefore, converting enzyme inhibitors, such as enalapril, provide useful adjunctive therapy in diuretic-treated patients, but potassium supplementation may be required before the start of four weeks of combined therapy.

Topics: Angiotensin-Converting Enzyme Inhibitors; Dipeptides; Diuretics; Electrolytes; Enalapril; Humans; Hydrochlorothiazide; Hyperaldosteronism; Hypokalemia; Random Allocation; Renin

This presentation is a summary of our recent clinical studies on the therapeutic use of a new potassium-sparing diuretic, amiloride, and a converting enzyme inhibitor, MK-421, in preventing hypokalemia associated with primary and secondary hyperaldosteronism. These drugs are quite different in their physiologic action but they both may be effective in preventing the potassium depletion associated with increased aldosterone production. Amiloride, which blocks the sodium channels in distal renal tubular cells, was administered to 10 patients with primary hyperaldosteronism and five patients with Bartter's syndrome (secondary hyperaldosteronism). Amiloride, at doses of 10-40 mg/day, increased mean plasma potassium levels in both primary hyperaldosteronism (3.2-4.5 mEq/L) and, to a lesser extent, in Bartter's syndrome (2.5-3.6 mEq/L). The blood pressure fell slightly but significantly in primary hyperaldosteronism (171/112 vs 150/97 mm Hg) and remained unchanged in Bartter's syndrome (116/80 vs 117/71 mm Hg). The plasma renin activity and plasma aldosterone rose in primary aldosteronism (PRA 0.39-2.21 ng A1/m1/h and PA 28.4-54.3 ng/d1); but in Bartter's syndrome, the PRA declined (25.3-11.9 ng A1/m1/h) and the PA rose (19.5-38.0 ng/d1). The discrepancy in the PRA between primary aldosteronism and Bartter's syndrome may be due to the effects of potassium repletion on suppressing renin and stimulating aldosterone; while in primary aldosteronism, a mild diuretic effect could explain the rise in PRA. In both of these disorders, despite the rise in plasma potassium levels, amiloride produced a counter-therapeutic rise in PA which could potentiate further potassium losses. Therefore, we undertook a study to evaluate the prevention of diuretic-induced hypokalemia and secondary hyperaldosteronism using a new converting enzyme inhibitor, MK-421. Eighteen normal subjects were randomized into three groups receiving either (1) hydrochlorothiazide alone (50 mg/day), (2) MK-421 alone (10 mg/day), or (3) hydrochlorothiazide (50 mg/day) plus MK-421 (10 mg/day). Although MK-421 did not prevent diuretic-induced hypokalemia or hyperaldosteronism in the first week, after that time hypokalemia was reversed and ASR returned to normal. In these studies, it therefore appears that while potassium-sparing diuretics may remain the medical mainstay in treating primary aldosteronism, new converting enzyme inhibitors such as MK-421 may be more effective in treating secondary hyperaldoster

Topics: Adult; Aged; Aldosterone; Amiloride; Angiotensin-Converting Enzyme Inhibitors; Dipeptides; Diuretics; Electrolytes; Enalapril; Female; Humans; Hydrochlorothiazide; Hyperaldosteronism; Hypokalemia; Male; Middle Aged; Pyrazines; Renin

Medical treatment with a mineralocorticoid receptor (MR) antagonist, which has produced spontaneous remission of bilateral primary aldosteronism (PA), may also produce spontaneous remission of unilateral PA, for which laparoscopic adrenalectomy is recommended. However, few reports exist regarding spontaneous remission after MR antagonist therapy in unilateral PA.. The aim of this paper is to report a case of unilateral PA with spontaneous remission and reduction of cardiac hypertrophy after long-term spironolactone (SP) therapy.. A 41-yr-old Japanese male was treated for hypertension and hypokalemia for 5 yr. Primary aldosteronism was diagnosed by a furosemide and upright posture test and a captopril challenge test. Computed tomography imaging showed a 5-mm left-sided adrenal mass. Adrenal vein sampling demonstrated overproduction of aldosterone from the left adrenal gland. Long-term treatment with SP normalized the plasma aldosterone concentration. After discontinuation of SP, the patient's blood pressure, serum potassium level, and plasma aldosterone concentration remained in the normal range. The associated cardiac hypertrophy also improved and continued to resolve even after discontinuation of SP. Although the left adrenal gland tumor was still present on computed tomography after treatment, a furosemide and upright posture test, a captopril challenge test, and a saline loading test produced no evidence of PA. Adrenal vein sampling demonstrated no sign of lateralization.. These results demonstrate that SP not only antagonizes the MR, but also decreases aldosterone synthetic activity, which may produce remission in some patients with unilateral PA.

Topics: Adrenal Gland Neoplasms; Adult; Aldosterone; Antihypertensive Agents; Cardiomegaly; Enalapril; Humans; Hyperaldosteronism; Hypertension; Male; Mineralocorticoid Receptor Antagonists; Remission Induction; Spironolactone; Tumor Burden

A 77-year-old man with a history of hypertension and hyperuricemia was admitted to our hospital complaining of limb weakness, persistent constipation, and worsening hypertension. He had been taking a Chinese herbal remedy for allergic rhinitis for the past 10 years, together with an angiotensin-converting enzyme inhibitor (ACE-I; enalapril, 20 mg daily). After the dosage of enalapril had been reduced to 10 mg daily about 1(1/2) years before the current admission, he had developed persistent constipation. Therefore, he had started taking another traditional Chinese herbal remedy, a laxative, for the constipation, about 4 months prior to this hospitalization. Laboratory data on admission demonstrated marked metabolic alkalosis with severe hypokalemia associated with urinary wasting of potassium and chloride. A diagnosis of pseudoaldosteronism was made based upon his past history of exposure to various traditional Chinese medicines containing glycyrrhizin. Discontinuation of the Chinese remedies and supplementation of potassium successfully normalized the electrolyte imbalance and relieved all symptoms within a short time. The present case describes the occurrence of pseudoaldosteronism induced by a patient taking two traditional Chinese herbs, both containing glycyrrhizin, resulting in an overdose of this causative chemical agent. The development of pseudoaldosteronism appeared to be of particular interest with regard to the interaction of the renin-angiotensin-aldosterone (RAA) system with glycyrrhizin, in which an ACE-I retarded the development of pseudoaldosteronism.

Topics: Angiotensin-Converting Enzyme Inhibitors; Cathartics; Constipation; Drugs, Chinese Herbal; Enalapril; Glycyrrhizic Acid; Herb-Drug Interactions; Humans; Hyperaldosteronism; Hypertension; Male; Potassium; Rhinitis, Allergic, Perennial

A 66-year-old hypertensive diabetic patient with latent hypoaldosteronism and mild renal failure was treated by adding enalapril, an angiotensin converting enzyme inhibitor, to the furosemide and nifedipine regimen because of an insufficient antihypertensive response for 1 month. Seven days after enalapril addition, the blood pressure was significantly reduced, but frank hyperkalemia occurred with a marked rise in BUN and a slight increase in serum creatinine. Plasma renin activity (PRA) and plasma aldosterone (PA) values remained low before and during enalapril therapy. Transient treatment with sodium polystyrene sulfate after enalapril withdrawal improved the hyperkalemia and renal function, but PRA and PA levels were low. PA and its precursor steroids also responded poorly to graded angiotensin II infusion and rapid ACTH injection. Latent hypoaldosteronism probably predisposed this patient to frank hyperkalemia with progressive dehydration and slightly reduced renal function during antihypertensive therapy.

Topics: Aged; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Drug Therapy, Combination; Enalapril; Furosemide; Humans; Hyperaldosteronism; Hyperkalemia; Hypertension; Kidney Failure, Chronic; Male; Nifedipine

This is the first reported case of the idiopathic type of primary aldosteronism in pregnancy. The severely hypertensive patient was unresponsive to treatment with high doses of four antihypertensive agents administered concurrently. A drastic improvement in blood pressure was noted within 24 hours of beginning enalapril maleate, although subsequent deterioration in fetal status led to delivery at 26 weeks' gestation. Alternatives to standard medical therapy may be necessary for this rare but potentially life-threatening disease during pregnancy.

Topics: Adult; Antihypertensive Agents; Cesarean Section; Drug Therapy, Combination; Enalapril; Female; Humans; Hyperaldosteronism; Hypertension; Infant, Newborn; Pregnancy; Pregnancy Complications; Pregnancy Complications, Cardiovascular

Topics: Adult; Bartter Syndrome; Enalapril; Humans; Hyperaldosteronism; Long-Term Care

Seven patients with Bartter's syndrome were investigated before and after 3 months' treatment by enalapril. Serum potassium rose from 2.4 +/- 0.5 to 3.9 +/- 0.6 mmol/L. In all patients, serum magnesium rose and bicarbonate fell. Hormonal changes were as suspected: a further stimulation of renin and a decline in aldosterone. The BP sensitivity to angiotensin II normalized in the five patients in whom the test was performed. Clearance studies during maximal water diuresis, performed in four patients, were compatible with a high proximal fractional tubular sodium reabsorption and a relatively low distal fractional sodium reabsorption. Fractional free water excretion after furosemide was also low, confirming the concept of a primary sodium reabsorption defect in the furosemide-insensitive part of the nephron in Bartter's syndrome. The only consistent change after enalapril was a further decline in distal fractional sodium reabsorption. Initiation of therapy produced a BP fall in each subject. Clinical important hypotension associated with oliguria was seen twice, but these reactions were short-lasting. The BP rose to pretreatment values within 72 hours, despite continuation of converting-enzyme inhibition. Renal function recovered, though a moderate fall in function persisted. No other side effects were noticed. We conclude that converting-enzyme inhibition improves the potassium metabolism of patients with Bartter's syndrome, without ameliorating the abnormal renal sodium handling.

Topics: Adult; Bartter Syndrome; Electrolytes; Enalapril; Extracellular Space; Female; Humans; Hyperaldosteronism; Hypokalemia; Male; Middle Aged; Renin-Angiotensin System; Sodium

Total Body Potassium (TBK) was measured by whole body counting of 40K in 3 patients with Bartter's syndrome before, after 3 months and after 1 year of treatment with enalapril. In 2 patients TBK was found to be decreased before treatment, whereas TBK was within the normal range in the 3rd. During treatment serum potassium concentration and TBK increased in each subject and symptoms of fatigue and tetany disappeared. Enalapril is shown to be an effective treatment in Bartter's syndrome as it improves serum potassium, TBK and complaints.

Topics: Adult; Bartter Syndrome; Enalapril; Female; Follow-Up Studies; Humans; Hyperaldosteronism; Hypokalemia; Male; Middle Aged; Potassium

Patients with idiopathic hyperaldosteronism (IHA) manifest hypertension, hypokalemia, and renin suppression. IHA is thought to have one of three possible etiologies: zona glomerulosa autonomy, an aldosterone secretory factor, or angiotensin-II (A-II) adrenal hypersensitivity. To determine the contribution of A-II adrenal hypersensitivity in IHA, four patients with IHA were treated with a new angiotensin-converting enzyme inhibitor, enalapril, on a controlled diet (sodium [128 mEq/day] and potassium [80 mEq/day]) in a metabolic unit. The results of this study demonstrate that enalapril therapy in three of four patients normalized blood pressure, improved potassium balance, elevated PRA, reversed the postural increment in plasma aldosterone concentration (PAC), and reduced aldosterone secretion to normal. The fourth patient with bilateral macronodular disease, on the other hand, had no improvement in any of the above indices, despite maximal doses of enalapril (80 mg/day). This patient, however, may have had bilateral adrenal adenomas, based on extremely elevated 18-OH-corticosterone levels (greater than 100 ng/dl), and because of a lack of adrenal A-II hypersensitivity, demonstrated by a fall in pre-enalapril, postural-, and lasix-induced PAC. In conclusion, enalapril improved the hypertension, hypokalemia, renin suppression, and hyperaldosteronism in three patients with IHA over 28 days of therapy. The results of this study suggest an etiologic role of A-II adrenal hypersensitivity in IHA.

Topics: Adult; Enalapril; Female; Humans; Hyperaldosteronism; Middle Aged

Effects of MK 421, a new angiotensin-converting enzyme inhibitor, were studied in normal men and patients. MK 421 was given at 0900 h as a single oral dose of 20 mg, to 5 normal men and 2 patients with essential hypertension and 10 mg to a patient with Bartter's syndrome, in the recumbent position. In all of them blood pressure (BP) fell, plasma angiotensin I (Pl AI) and plasma renin activity (PRA) increased, and plasma aldosterone (PA) decreased from 2 h to 6 h. Maximum effects were observed at 4 or 6 h. Then the effects attenuated gradually but still remained at 24 h. In the same 5 normal men angiotensin I (AI) was infused iv at a rate of 20 ng/kg . min from 0900 h to 1500 h, from 2030 h to 2100 h, and the next morning from 0830 to 0900 h. At first the BP rose and PA increased. The onset of the BP fall was at 35, 55, 60, 70 and 85 min in each subject, respectively. Then the BP and PA began to decrease and the Pl AI and PRA began to increase. The maximum effects were observed at 4 or 6 h. Then these inhibitory effects on the AI were attenuated but still remained at 24 h. The 2 patients with essential hypertension and a patient with malignant hypertension was treated with MK 421 at a daily doses of 5 to 40 mg for 2 to 6 months. They all showed a fall in BP and no side-effects were noted. From these results it is concluded that MK 421 is a strong and long-acting antihypertensive drug and its clinical application seems very useful for the treatment of hypertension.

Topics: Adult; Aldosterone; Angiotensin I; Antihypertensive Agents; Bartter Syndrome; Blood Pressure; Dipeptides; Enalapril; Humans; Hyperaldosteronism; Hypertension; Hypertension, Malignant; Male; Middle Aged; Renin