1. The role of Ca 2+ in the control of renin release was investigated using a collagenase-dispersed rat kidney cortex cell preparation. 2. Superfusion with a series of low [Ca 2+ ] buffers in either ascending or descending order of concentration increased renin release. Exposure to 0.06 mmol/l Ca 2+ increased release by 120% ( P < 0.001) when presented as the first buffer in ascending order of concentration and by 79% ( P < 0.001) when presented as the fourth and last in a series of descending order. 3. The Ca 2+ entry blocking drug diltiazem in a range of concentrations increased renin release and at 10 −5 mol/l diltiazem the mean stimulation was 35% ( P < 0.01). 4. 8-( N,N -Diethylamino)octyl-3,4,5-trimethoxybenzoate (TMB-8) reduces the release of Ca 2+ from intracellular stores and, studied over a range of concentrations, this compound increased renin release. At 10 −5 mol/l TMB-8 the mean increase was 44% ( P < 0.001). 5. None of these experimental manipulations, low [Ca 2+ ], diltiazem or TMB-8, had any effect on the release of adenosine 3′:5′-cyclic monophosphate into the cell superfusate, indicating that a decrease in intracellular [Ca 2+ ] increases renin release by a mechanism which is independent of changes in adenosine 3′:5′-cyclic monophosphate production. 6. Effects of low [Ca 2+ ], diltiazem and TMB-8 on renin secretion were all shown to be reversible when superfusion with control buffer was resumed.

1. The effect of the β-adrenoceptor agonist isoprenaline on the secretion of active and inactive renin was investigated in two preparations. 2. in ten urethane-anaesthetized rabbits isoprenaline, given as a renal artery infusion, had relatively minor effects on renal sodium excretion (increased) and systemic arterial blood pressure (decreased). Urine volume, potassium excretion, creatinine clearance and serum electrolytes were all unchanged. Plasma active and inactive renin both increased immediately and returned to basal values after ceasing the isoprenaline infusion. 3. No significant changes in either plasma renin activity or renal function were observed in a group of ten control animals. 4. The magnitude of the isoprenaline-induced changes in plasma active renin was similar to that in a previous study of frusemide diuresis, but the time course was quite different. Inactive renin disappeared from plasma during frusemide diuresis. 5. Renin release by rabbit kidney cortex slices was also studied. Isoprenaline, added to the incubation medium, caused a dose-related increase in active renin secretion, but inactive renin release remained unchanged. This is in marked constrast to a previous study where reducing [Na + ] increased active renin and inhibited inactive renin output. 6. These data support our previous suggestion that activation of inactive renin is regulated by a sodium-sensitive intrarenal mechanism.

1. An inactive form of renin exists in rabbit plasma. This can be activated, and therefore measured, after acidification (pH 2.8). 2. The effect of frusemide diuresis, with replacement of volume losses, on plasma levels of active and inactive renin was studied over a 3 1/2 h time course. Plasma active renin increased during frusemide diuresis but inactive renin disappeared from the circulation. The time courses for the changes in the two forms of renin were similar. 3. The peak of the frusemide-induced changes in renal function (urine flow, sodium and potassium excretion and creatinine clearance) preceded the maximum changes in the two forms of renin by 90 min. 4. The response of plasma levels of inactive renin to physiological stimuli depends on the nature of the stimulus, as well as its duration. Some form of sodium-sensitive mechanism may control the activation of inactive renin.

1. Renin activity in rabbit plasma increases after acidification (pH 3·3), probably due to activation of an inactive form of renin. 2. Both active and inactive renin in plasma increase after haemorrhage. This stimulus does not change the relative proportions of the two forms. 3. After ligation of the renal blood vessels neither form of renin increases in response to haemorrhage. 4. One day after bilateral nephrectomy no inactive renin could be demonstrated in plasma. 5. In the rabbit, therefore, the kidney is a major source of the inactive renin in plasma.