ABSTRACT
UK 69 578 is a competitive inhibitor of endopeptidase 24.11 (the enzyme that degrades atrial natriuretic factor) in vitro. In vivo, UK 69 578 has renal and cardiovascular effects similar to low-dose atrial natriuretic factor infusion, and may be a useful agent in hypertension and heart failure.
Subject(s)
Atrial Natriuretic Factor/antagonists & inhibitors , Cyclohexanecarboxylic Acids , Neprilysin/antagonists & inhibitors , Animals , Atrial Natriuretic Factor/blood , Clinical Trials as Topic , Coronary Disease/blood , Coronary Disease/drug therapy , Dogs , Dose-Response Relationship, Drug , Double-Blind Method , Drug Evaluation , Drug Evaluation, Preclinical , Half-Life , Humans , Infusions, Intravenous , Male , Middle Aged , Natriuresis/drug effects , Nephrectomy , Neprilysin/blood , Neprilysin/pharmacology , Rats , Rats, Inbred Strains , Time FactorsABSTRACT
The whole body content of sodium, potassium, chlorine, calcium, phosphorus and nitrogen was measured by neutron activation analysis in 13 patients with untreated primary hyperaldosteronism (Conn's syndrome; aldosterone-secreting adenoma). Concurrently, exchangeable sodium and potassium were estimated by isotope dilution. Results were compared with values in the same patients during treatment with potassium-conserving diuretics and again after removal of the adenoma; and also with those in a series of 30 patients having untreated essential hypertension. Both total body and exchangeable sodium were high in Conn's syndrome before treatment and were reduced by spironolactone or amiloride and by subsequent surgery. There was no evidence of alteration in the proportion of non-exchangeable sodium in this disease, in contrast to earlier reports. Total body and exchangeable potassium were low in untreated Conn's syndrome and increased to normal after therapy: the proportion of non-exchangeable potassium was similar before and after treatment, and also similar to that in essential hypertension. Total body chlorine was increased before treatment in Conn's syndrome and returned to normal with therapy; body calcium, phosphorus and nitrogen were normal throughout.
Subject(s)
Body Composition/drug effects , Chlorine/metabolism , Hyperaldosteronism/metabolism , Potassium/metabolism , Sodium/metabolism , Adult , Aged , Calcium/metabolism , Female , Humans , Hyperaldosteronism/drug therapy , Male , Middle Aged , Neutron Activation Analysis , Nitrogen/metabolism , Phosphorus/metabolismABSTRACT
The whole body content of sodium, chlorine and potassium has been measured in 30 patients with essential hypertension, using the techniques of in vivo neutron activation analysis and whole body counting. Total exchangeable sodium and potassium were also measured, and found to be well correlated with the total body amounts of these elements. Comparable measurements on normotensive subjects could not be obtained, but results for both elements were similar to those expected on the basis of published values for healthy normal body composition. Similarly, no abnormality was found in the average body content of the other major elements (chlorine, calcium, phosphorus and nitrogen). We therefore have no evidence that essential hypertension is associated with any abnormality in the mean body content of these elements. However, there was some evidence of a relationship between body sodium and blood pressure in this study group.
Subject(s)
Hypertension/metabolism , Potassium/analysis , Sodium/analysis , Adult , Aged , Body Composition , Calcium/analysis , Chlorine/analysis , Female , Humans , Male , Middle Aged , Neutron Activation Analysis , Nitrogen/analysis , Phosphorus/analysis , Whole-Body CountingABSTRACT
A patient, who presented with a flaccid quadriplegia due to profound hypokalaemia, is described. Hypokalaemia and myoglobinuria were caused by the ingestion of small amounts of liquorice contained in a laxative preparation. Subsequent controlled administration of small amounts of this preparation induced marked hypokalaemia. This was associated with sodium retention and potassium loss confirming a mineralocorticoid-like action. The sodium retention was associated with suppression of plasma levels of renin and aldosterone.
Subject(s)
Glycyrrhiza , Hypokalemia/etiology , Plants, Medicinal , Quadriplegia/etiology , Aged , Cathartics/adverse effects , Female , Humans , Hypokalemia/metabolism , Myoglobinuria/etiology , Potassium/metabolism , Sodium/metabolismABSTRACT
1. Total-body neutron-activation analysis in vivo was carried out in 11 hypertensive subjects to measure simultaneously the total body content of sodium, chlorine, calcium, phosphorus and nitrogen. 2. There was a highly significant correlation between total body sodium measured by activation analysis and total exchangeable sodium measured by a standard isotope-dilution technique (r = 0.92, P less than 0.001). Exchangeable sodium averaged 80.3% of total body sodium. 3. The measured values of chlorine, calcium, phosphorus and nitrogen were similar to those for healthy subjects reported by others. 4. Activation analysis in vivo appears promising as an additional tool for investigating sodium metabolism in hypertension, as it is the only method available for determining the total body content of this element. The radiation dose (1 rem) is sufficiently low to permit repeated measurements in the same subject.