1. 11β-Hydroxysteroid dehydrogenase is an enzyme complex consisting of 11β-dehydrogenase and 11-oxoreductase responsible for the interconversion of cortisol to cortisone in man. Inhibition of 11β-dehydrogenase (e.g. after liquorice ingestion) results in cortisol acting as a potent mineralocorticoid. We have evaluated the effect of the synthetic liquorice derivative, carbenoxolone, on this enzyme complex. 2. Carbenoxolone given to six volunteers in metabolic balance produced sodium retention with suppression of the renin-angiotensin-aldosterone system. Plasma potassium fell, although there was no kaliuresis. This was associated with inhibition of 11β-dehydrogenase (as measured by a rise in the plasma half-life of [11α- 3 H]-cortisol). Unlike liquorice, however, carbenoxolone also inhibited 11-oxoreductase (as measured by the generation of cortisol after oral cortisone acetate). 3. The mineralocorticoid activity of carbenoxolone, like liquorice, is mediated via cortisol by inhibition of 11β-dehydrogenase. Carbenoxolone, however, also inhibits 11-oxoreductase activity and this may relate to its effect on renal potassium excretion.

1. A dynamic column superfusion system has been developed for the study of renin secretion in rat renal cortical cells. 2. Cells were isolated by collagenase digestion and mechanical dispersion, before suspension with polyacrylamide beads and superfusion with oxygenated physiological medium. 3. Renin was detected in the superfusate by incubation of fractions with excess nephrectomized sheep substrate in the presence of angiotensinase inhibitors followed by radioimmunoassay of the angiotensin I generated. 4. Optimized methodology included a purposebuilt polytetrafluorethylene flow cell, a 1 h equilibration to achieve a steady state, 5 min eluate collections, a 15 min stimulatory and a 30 min recovery period, and duration of perfusion of up to 270 min. 5. Significant increments above baseline renin release were seen with the stimuli of adrenaline, noradrenaline and isoprenaline. These could be demonstrated with concentrations of 10 −9 mol/l (adrenaline), 5 × 1O −10 mol/l (noradrenaline) and 1O −9 mol/l (isoprenaline). 6. This technique has significant advantages over previous methods for the study of renin secretion in vitro at the cellular level. It is reproducible and sensitive, and avoids many of the limitations of static cell suspension and kidney slice methods.

1. The mineralocorticoid activity of 18-hydroxycorticosterone (18-OH-B) has been compared with that of aldosterone by using human bioassay in vivo with measurement of rectal potential difference and urinary log 10 Na + /K + ratio. 2. A log-linear relationship was found between maximum change in rectal potential difference and increasing doses of aldosterone. 3. No mineralocorticoid activity could be demonstrated after an intravenous bolus and infusion of 18-OH-B. 4. The half-life of clearance of 18-OH-B was measured in three subjects and found to be 28, 48 and 24 min.