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1. Dietary sodium depletion and subsequent repletion was studied in rabbits. Potassium intake was maintained constant. 2. during sodium depletion and repletion blood pressure, packed cell volume, food consumption and body weight remained at control values. 3. Decreased sodium excretion was observed in both urine and faeces during sodium depletion and the physiological control of these changes is discussed in relation to the renin-angiotensin-aldosterone system. 4. Potassium excretion during sodium depletion initially fell as a result of reduced urine volume and gradually returned to normal. Urine potassium concentration remained constant. 5. Faecal excretion of potassium rose by 63% during sodium depletion and there was a rise from a control value of 17-25% in the proportion of total potassium excretion accounted for by the faecal component. 6. Water consumption and urine volume both decreased in the initial phase of sodium depletion and then returned to control levels. 7. It is important to consider both urinary and faecal excretion of sodium and potassium when calculating balance status for either ion. Faecal excretion, as well as kidney function, shows important physiological adaptations.

Excitation-secretion coupling for active and inactive renin was investigated by manipulating the ionic composition of media in which rabbit kidney cortex slices were incubated. Alterations in [Ca++] and [K+] produced qualitatively similar, but quantitatively distinct, changes in the release of the two forms of renin. Under control conditions, the slices secreted 15-20% of total renin in the inactive form and exposure to Ca++-free or low [K+] media increased this to 30-40%, a similar proportion to that stored within the kidney. Decreasing [Na+] stimulated release of active renin but reduced inactive renin. There appeared to be antagonism between the effects of Na+ and Ca++ ions in respect of active renin but synergism for release of the inactive form. It is suggested that the characteristics of a single renin release mechanism in the rat kidney resemble those for secretion of inactive, rather than active, renin in other species.

The presence of calcium in the fluid in which intestinal or kidney tissue is incubated is required for the tissue to respond to angiotensin. Everted sacs of rat colonic mucosa exhibited an increased rate of fluid transport in the presence of angiotensin; this response was lost when the serosal fluid, but not the mucosal fluid, was calcium-free. Angiotensin-stimulated transport was maintained when calcium was replaced with strontium or barium, but was lost when calcium was exchanged for magnesium. Similarly, calcium ions were required in the incubation fluid of rat kidney cortex slices to demonstrate angiotensin-enhanced sodium transport. These observations are discussed in relation to the possible roles of divalent cations in the mechanism of action of angiotensin.

1. Active and inactive renin release by rabbit kidney cortex slices was investigated. Inactive renin was estimated as the increase in renin activity after acidification (pH 2 . 8) of slice supernatant solutions. 2. Active renin release was increased when incubation medium [Na+] was reduced. This relationship was linear (r2 = 0 . 96) over the range [Na+] = 23-133 mM. 3. For the same range of [Na+] inactive renin secretion decreased when medium [Na+] was reduced (r2 = 0 . 92). Therefore, the proportion of total renin which was in the inactive form decreased linearly as [Na+] was reduced (r2 = 0 . 97). 4. Chloride ions did not appear to be important in altering the secretion of either active or inactive renin. 5. Adding furosemide to the incubation medium in concentrations up to 40 micrograms/ml. did not change secretion of either form of renin. The action of furosemide on secretion of active and inactive renin in vivo is therefore secondary to altered renal function. 6. Regulation of the relative amount of active and inactive renin in plasma could be entirely an intrarenal event. It is not essential to invoke a plasma activating enzyme for inactive renin in order to explain changes in plasma levels of the two forms of renin. 7. This paper supports the hypothesis that release of inactive renin by the kidney is controlled by a sodium-sensitive mechanism.

1. Active and acid-activatable (inactive) renins were measured in rabbit plasma under control conditions and during sodium depletion with subsequent repletion. 2. Active renin increased by 97% during sodium depletion and returned to control levels on repletion. Both changes were complete within 1 day of changing the diet. 3. During dietary sodium depletion inactive renin levels initially fell to zero and then increased until, after 13 days, inactive renin was again 10% of total renin levels, a proportion comparable to the control values. 4. Sodium repletion caused plasma inactive renin to return to control levels over about 13 days, a quite different time course to active renin. Therefore, in the first phase of repletion the proportion of total renin in the inactive form rose to 19%. 5. These changes are discussed in relation to concurrent changes in sodium, potassium and water metabolism.

1. A study has been made of the effect of angiotensin (10(-12) g/ml.) on active and passive transport of sodium, potassium and water between rat kidney cortex slices and the incubation medium.2. Angiotensin has no effect on the passive uptake of sodium and loss of potassium by slices incubated under conditions which inhibit active transport.3. Active sodium extrusion by slices incubated under aerobic conditions is stimulated, whereas active potassium uptake is inhibited by angiotensin.4. Sodium pump activity is stimulated by angiotensin in the presence of ouabain or in the absence of potassium in the incubation medium, conditions which block the sodium for potassium exchange pump.5. There is a 2 min latent period following the application of angiotensin before a response is observed.6. These findings are discussed in relation to the mechanism of action of angiotensin on kidney sodium and fluid transport processes.

1. Mucosal water and sodium transfer were measured in everted sacs of rat jejunum.2. There was no effect on mucosal water and sodium transfer when aldosterone was added to the incubation medium.3. An 87% increase in mucosal water and sodium transfer was obtained in sacs prepared from animals maintained on a low sodium diet compared to sacs from animals on a normal diet.4. Injection of 5 mug aldosterone intraperitoneally to animals maintained on a high sodium diet produced a significant increase in mucosal water and sodium transfer in sacs prepared 27 hr later and this was still present 36 hr after injection.5. The aldosterone-induced rise in mucosal water transfer was blocked if actinomycin D was administered one hour before the aldosterone injection.6. It is suggested that aldosterone action on sodium and water transport in rat jejunum is mediated through a primary action on protein synthesis and that the long delay can be explained in terms of gut morphology.

1. A study has been made of the effects of cyclic AMP, phosphodiesterase inhibitors and protein synthesis inhibitors on the response of rat kidney cortex slices to physiological doses of angiotensin.2. The additions of cyclic AMP, dibutyryl cyclic AMP and/or phosphodiesterase inhibitors to the incubation medium (conditions which would be expected to increase intracellular cyclic AMP levels) were without effect on sodium or potassium transport by kidney slices.3. Actinomycin D (an inhibitor of the transcription stage of protein synthesis), at concentrations which inhibit RNA synthesis by 75%, has no effect on either control or angiotensin stimulated sodium transport.4. Cycloheximide or puromycin (inhibitors of the translation stage of protein synthesis), at concentrations which inhibit protein synthesis by 70-80%, have no effect on control sodium and potassium transport by kidney slices, but completely block the angiotensin stimulation of these processes.5. These findings are discussed in relation to the possible involvement of cyclic AMP and protein synthesis in the mechanism of action of angiotensin on kidney sodium and potassium transport.