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The clinical use of angiotensin converting enzyme inhibitors in hypertension and cardiac failure.

The renin-angiotensin system has a range of physiological actions concerned with the control of the circulation. Angiotensin II has both an immediate and a delayed pressor effect, it stimulates the secretion of aldosterone and antidiuretic hormone, promotes thirst, stimulates the sympathetic nervous system at various sites while inhibiting vagal tone, and has a range of direct effects on the kidney. Several aspects of this range of actions can become deranged in a number of forms of hypertension as well as in congestive cardiac failure. Hence much effort has been directed in recent years to the development of agents designed to interfere with the renin-angiotensin system and to apply these clinically in the treatment of hypertension and congestive cardiac failure. Orally active converting enzyme inhibitors are of proven benefit not only in renovascular hypertension, but also, when combined with loop diuretics, in the treatment of intractable hypertension as well as, both alone and in combination with thiazide diuretics, in the treatment of essential hypertension. In congestive cardiac failure controlled trials have shown that converting enzyme inhibitors can improve exercise tolerance while diminishing lassitude, correct potassium deficiency and limit ventricular arrhythmias. Energetic efforts are being made to develop orally active inhibitors of the enzyme renin itself, since these would be more specific in action than the presently available and very successful converting enzyme inhibitors.

Angiotensin-Converting Enzyme Inhibitors↗

[State of water-electrolyte metabolism in ischemic heart disease].

The state of the water-electrolyte metabolism was studied by the radio-isotope dilution technique in 115 patients with different forms of ischaemic heart disease and in 25 normal persons. It was established that all forms of ischaemic heart disease are accompanied by a significant potassium deficit imperceptible for blood and urine examinations of their electrolyte composition. The potassium deficit is most clearly expressed in patients with cardiosclerosis, especially in congestive heart failure. In a considerable part of the patients with acute myocardial infarction, including those without clinical signs of congestive heart failure, the rate of sodium and water metabolism is decreased, and the total body content of metabolizing sodium is increased. Sodium retention in the body is especially severe in patients with cardiosclerosis complicated by congestive circulatory insufficiency. The administration of diuretics in adequate doses was shown to result in normalization of the indices of sodium and water metabolism.

Adult↗

[Renal insufficiency and diabetes cured by removal of a villous tumor of the rectum].

A case of villous tumour of the rectum presenting in a misleading fashion : clinically, an apparent adrenal insufficiency and biologically renal insufficiency and diabetes. The abnormal glucose metabolism was attributed to potassium deficiency. The conditions and frequency of occurence of hydroelectrolytic problems in association with villous tumours and the various presenting features, some misleading, are discussed. The difficulties of diagnosis and treatment are emphasised.

Adenoma↗

[Renal effects of the acute inhibition of angiotensin-converting enzyme. I. 2) Studies during moderate potassium depletion].

We have investigated the relative roles of angiotensin II on the renal function and urinary excretion of some prostanoids in healthy women submitted to different conditions of potassium balance. To this aim we have evaluated the effects of an acute inhibition of angiotensin converting enzyme by enalapril (E). The renal function was explored by clearance (cl.) method during induced hypotonic polyuria (oral water load followed by 5% dextrose solution infusion). During 60 min cl. period the urinary PGE2, 6-keto-PGF1 alpha and TxB2 were determined by RIA method. Each subject received paired studies, in absence and presence of E (10 mg administered per os 1 hour before the water load). Basal values of plasma renin activity (PRA) and urinary aldosterone (excreted during the 24 hours before the water load) were also determined by RIA method. This study protocol was applied in normal potassium balance (n = 6) and induced moderate potassium depletion (n = 6). This paper concerns the group in potassium depletion in both absence (D4) and presence of E (D4.E). Potassium depletion was induced by adaptation to a normal sodium (150 mmol/d) and low potassium (< or = 10 mmol/d) dietary intake combined to natriuretic treatment. The water and NaCl net losses were restored by 0.9% NaCl solution infusion. The cumulative potassium deficit achieved at the end of the depletive treatment was 214 +/- 54 mmol. This treatment induced significant decrease in basal plasma potassium concentration and increase in PRA without affecting urinary aldosterone and plasma sodium concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldosterone↗

[Morphogenesis of immune complex glomerulonephritis].

Morphological changes in the kidneys in nonspecific ulcerative colitis were studied and the following variants of the kidney involvement were established: (1) allergic changes manifested by membraneous and mesangio-proliferative glomerulonephritis, renal vasculitis, phenomena of stromal desorganization with lymphoid and histiocyte infiltrations; (2) metabolic changes manifested by various kinds of degeneration of the tubular apparatus including changes typical of potassium-deficient nephropathy; (3) toxic -- necrotic nephrosis and (4) infectious -- nonsuppurative and suppurative interstitial nephritis.

Glomerulonephritis↗

Mapping of QTLS for ferrous iron toxicity tolerance in rice (Oryza sativa L.).

Ferrous iron toxicity is the main factor limiting the productivity of rice in gleyic paddy soils. In this study, an F2 and an equivalent F3 populations derived from a japonica/indica cross of rice, Longza8503/IR64, were raised under iron-enriched solution cultures, and used to map QTLs controlling ferrous iron toxicity tolerance. A genetic linkage map consisting of 101 SSR markers was constructed to determine the position and nature of quantitative trait loci (QTLs) affecting Fe2+ toxicity tolerance. Three characters, i.e., leaf bronzing index (LBI), plant height (PH) and maximum root length (MRL) were evaluated for the F2 plants and F3 lines and the parents at the seedling stage in nutrient solution. A total of 20 QTLs for LBI, PH and MRL under the Fe2+ stress were detected over 10 of the 12 rice chromosomes, reflecting multigenic control of these traits. QTLs controlling LBI were located at the region of RM315-RM212 on chromosome 1, RM6-RM240 on chromosome 2 and RM252-RM451 on chromosome 4. Compared with other mapping results: (1) the QTL for LBI located at the region of RM252-RM451 on chromosome 4 was identical with the QTL for decreased chlorophyll content on a rice function map. Another QTL for LBI located at the region of RM315-RM212 on chromosome 1 was linked with the QTL for chlorophyll content which located at the region of C178-R2635 on a rice function map. (2) The third QTL for LBI located at the region of RM6-RM240 on choromosome 2 was linked with the QTL for potassium uptake located at the region of RZ58-CDO686 under potassium deficiency stress.

Chromosome Mapping↗

[Striatal syndrome and hypokalemia].

The authors present the case of a patient with a striated syndrome resembling Wilson's disease but without the disorder of cooper metabolism. The clinical picture was completely masked by a hypokalemia at 1 mEq/l following urinary loss of this cation, due to ascending interstitial nephritis. Correction of the potassium deficiency produced rapid reappearance of the initial neurological syndrome.

Athetosis↗

Heat stroke and related heat stress disorders.

Medical disorders related to environmental heat exposure are exceptionally common in persons who perform hard work in hot climates. They are also common in competitive athletes as well as in persons who participate in casual exercise to maintain health. The important issue of salt and water disturbances consequent to heavy sweating in hot climates is discussed in detail as are mechanisms of potassium deficiency and its implications. The major forms of environmental heat illness including heat syncope, heat cramp, heat exhaustion, and heat stroke are presented in detail with relevant clinical examples. A discussion of the differential diagnosis of hyperthermia and rhabdomyolysis follows. Because of the difference in treatment and complications, heat stroke is subdivided into the classic variety that affects the elderly and very young and that form that follows heavy physical work and is always associated with rhabdomyolysis. Because severe heat exhaustion and heat stroke are life-threatening disorders, the chapter includes a detailed discussion of complications and plans for treatment.

Animals↗

Treatment of hypercalcemia.

Severe hypercalcemia is a potentially life-threatening complication of several diseases. Most commonly it is caused by cancers that enhance bone resorption. Impaired renal calcium excretion resulting from a combination of volume contraction and calcium-induced renal injury (nephrocalcinosis) plays a critical role in the genesis and aggravation of hypercalcemia. Treatment of hypercalcemia is based on treating the underlying disease, restoring extracellular volume, correcting electrolyte deficiencies (potassium and magnesium), and reducing bone resorption. Several measures are available to reduce bone resorption, of which the most efficacious are the bisphosphonates and plicamycin (mithramycin). One of these agents in combination with volume expansion can reduce serum calcium concentrations to near normal in most patients within 3 to 6 days. Because of the delayed hypocalcemic action of these agents, they should be administered early. Calcitonin has a more modest hypocalcemic action than the bisphosphonates or plicamycin but has a more rapid effect. Combining calcitonin with plicamycin or a bisphosphonate can enhance the rate of decline of the serum calcium level. Bone resorption also can be reduced by getting patients out of bed to stand or walk. Glucocorticoids may be effective in patients with hypercalcemia associated with high levels of vitamin D, such as sarcoidosis, some lymphomas, or vitamin D intoxication. Patients with mild to moderate hypercalcemia may be asymptomatic. Therapy in these patients should be directed at the primary disease as well as at preventing complications that could raise the level of serum calcium. Efforts should be made to prevent volume contraction and prolonged bed rest. Sedatives and narcotic analgesics, by reducing activity and oral intake, can raise serum calcium levels. In the future it may be possible to predict which patients with cancer are likely to develop accelerated local tumor-mediated or humorally mediated osteolysis. For example, high circulating levels of PTH-like peptides in patients with lung cancer might suggest a greater risk of developing hypercalcemia. These patients could be monitored more closely by periodically measuring urinary calcium. Another prophylactic approach would be to treat patients at risk of developing hypercalcemia with drugs, such as the bisphosphonates, that inhibit bone resorption.

Humans↗

[Pseudoaldosteronism caused by licorice. Review of the literature and description of 4 clinical cases].

Metabolic and toxic effects caused by prolonged daily ingestion of Liquorice are well known in the literature. Such acquisition doesn't seem to be known enough by practitioners and by common people. Besides active substances such as Glycyrrhizin , Liquorice contains even steroids similar to the adrenocortical ones; among these the most important is Beta-Glycyrrhetinic acid. This one, in vivo and in vitro, produces salt and water retention by means of a "DOCA-like" mineral-corticoid mechanism, and clear suppression of the Renin-Angiotensin-Aldosterone axis. A low plasmatic level of Renin and Aldosterone is a common feature. The clinical picture in many ways is similar to the primary Aldosteronism and for this reason the above mentioned syndrome is usually called "Pseudoaldosteronism". Symptoms and signs can be classified into the following main groups: symptoms linked with water and salt retention: oedemas, hypertension, cardiac involvement. Symptoms linked with serum Potassium depletion: asthenia, paralysis (due to Potassium deficiency), myopathy with myoglobinuria. The diagnosis is essential based on an accurate pharmacological dietetic history, aimed to recognise an excessive use of Liquorice (pure or more often as substitute) in the screening of hypertension with or without hypopotassemia. Finally, the more or less quick normalisation of blood pressure and biochemical signs--as an "ex juvantibus" criterion--is the most important reason for the diagnosis. After a wide survey of the literature, the clinical and biological picture in four patients with chronic Liquorice ingestion and Pseudoaldosteronism syndrome is described.

Adult↗