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The pharmacological actions of a diuretic drug, fenquizone have been investigated and its effects compared with well characterized diuretics in rats, mice and rabbits. Changes in sodium and potassium excretion and urine volume were similar in magnitude and duration to those of the thiazide diuretics over dose range 0·05–100 mg kg−1. Free water clearance in rabbits was decreased indicating an action at the cortical diluting site in the nephron and since free water reabsorption was relatively unaffected it appears unlikely to have actions at other sites. Calcium and phosphate excretion studies also suggested that the predominant effects are those occurring at the cortical diluting segment of the nephron. Additional parameters not affected by the drug were blood flow to the cortex and medulla of the kidney (and other major organs), plasma glucose concentration and plasma urate concentration.

SUMMARY Acute occlusion of the blood supply to the liver decreases inactivation of tritiated cortisol, corticosterone and aldosterone. In malnourished animals which had lost approx. 25% of their initial body weight, only cortisol inactivation was decreased.

Zugabe von Glibenclamid bei Alloxan induzierten, stark zuckerkranken Ratten vermindert den Gehalt freier Fettsauren im Blutplasma. Kein entsprechend antilipolytischer Effekt wurde bei Wiederholung des Experimentes beobachtet, wenn Chlorpropamid und Tolbutamid hundertfach starker als Glibenclamid verabreicht wurde.

Glomerular filtration rate (GFR), cardiac output, regional blood flow and kidney weight were measured in alloxan and streptozotocin diabetic rats at different times after the administration of diabetogen. A high GFR was found together with increased kidney weight and reduced blood flow.

Es wurden die Wirkungen von Chlorpropamid, Glibenclamid und Tolbutamid auf die Nieren wasserbelasteter normaler und diabetischer Ratten untersucht.

Isolated spontaneously beating atria from streptozocin diabetic rats were compared with those from controls. Diabetic atria were found to have reduced rates, increased forces of contraction and reduced sensitivity to the inotropic effects of noradrenaline, isoprenaline, tyramine and calcium. Positive chronotropic responses to tyramine were also reduced but those to noradrenaline and isoprenaline were increased suggesting that tyramine releasable stores of noradrenaline were reduced. Elevation of glucose concentration in the medium from 5·6 to 27 min resulted in a decrease of inotropic sensitivity to the agents used in both control and diabetic rat atria. Resting contractile force of control rat atria was reduced by the inclusion of either 22 niM 2-deoxyglucose, 10−3 i.u. insulin ml−1 or 5 mM acetate in the medium. The rate was also reduced by medium containing 2-deoxyglucose but increased by insulin. 2-Deoxyglucose also reduced inotropic but increased chronotropic sensitivity to isoprenaline. Possible mechanisms responsible for the changes observed are discussed.

1. Frusemide, in doses which were maximal or supramaximal in respect of its natriuretic, diuretic and kaliuretic properties, produced a dose dependent, transient hyperglycaemic response in the mouse.2. Bilateral nephrectomy resulted in a complete abolition of the hyperglycaemic response.3. The hyperglycaemic response was accompanied by a decrease in liver glycogen and was significantly attenuated by adrenalectomy, adrenal demedullation and pretreatment with dihydroergotamine (DHE).4. In the nephrectomized mouse frusemide treatment produced a marked reduction in intravenous glucose tolerance and a reduction in the plasma concentration of immunoreactive insulin following glucose administration. The drug had no detectable effect upon insulin sensitivity.5. Hydrochlorothiazide exerted no detectable effect on mouse blood sugar.6. Ethacrynic acid hyperglycaemia was obtainable after intraperitoneal or intramuscular injection, but not after intravenous injection. Intravenously administered ethacrynic acid exerted no effect upon intravenous glucose tolerance or insulin sensitivity in the nephrectomized mouse.

SUMMARY Using a radioactive isotope technique, water turnover (biological half-life of tritium, T½) has been determined in a number of endocrine deficient states in rats. Water turnover was decreased after adrenalectomy but restored to normal in animals kept on 0·9% NaCl solution. A number of glucocorticoid hormones (cortisone, hydrocortisone, prednisolone and dexamethasone) were also able to restore water turnover to normal in adrenalectomized rats. Water turnover was also decreased in rats which had been thyroidectomized 3–5 days previously, but in chronically thyroidectomized animals or those in which hypothyroidism had been produced by propylthiouracil treatment, no significant change in water turnover could be detected. Propylthiouracil-treated animals kept on 0·5% NaCl solution had an increased water turnover. Water turnover was increased in hypophysectomized animals.

Treatment of mice for 14 days with ethacrynic acid or frusemide (100 mg/kg daily orally) increased the fasting blood sugar and liver glycogen. Oral glucose tolerance was altered so that blood sugar concentrations in drug-treated groups were significantly above control values. The failure of the drugs to affect intravenous glucose tolerance and sensitivity to insulin or to tolbutamide suggested that the decrease in the oral glucose tolerance was attributable to some effect of the drug treatments on the rate of absorption of glucose from the gastrointestinal tract. Treatment with hydrochlorothiazide (100 mg/kg daily orally) exerted no effect on blood sugar, liver glycogen or glucose tolerance.