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1. Renal haemodynamic and tubular transport responses to low‐dose infusions (0.1‐5.0 ng min‐1) and injections (50‐200 ng) of atrial natriuretic factor (ANF) were studied in anaesthetized rats (average body weight, 300 g). 2. The lowest infusion dose (average, 0.3 ng kg‐1 min‐1) was above threshold for significant hypotension (‐11 mmHg), increased glomerular filtration (20%), urine flow (104%) and sodium output (191%). 3. Compared with the lowest rate of infusion of ANF, the smallest injection dose (50 ng) was less effective in reducing blood pressure, caused no change in glomerular filtration rate but induced similar diuresis and natriuresis. Based on total dose administered, sensitivity to injection was only one‐tenth that of infusion. 4. Absolute proximal reabsorption, derived from lithium clearance measurements, did not increase in parallel with filtration rate during infusions, and fractional proximal reabsorption was markedly depressed. Proximal glomerulo‐tubular balance was only 50% effective at 0.1 ng min‐1, falling to 16% at 5 ng min‐1. 5. Despite complete recovery of filtration rate and filtration fraction 30 min after terminating infusions, diuresis, natriuresis and depressed fractional proximal reabsorption persisted. Time‐control animals displayed no changes in renal function. 6. It is proposed that disruption of glomerulo‐tubular balance occurred in these experiments from inhibition of endogenous angiotensin II‐stimulated proximal sodium reabsorption by ANF. Persistence of this action may be due to accumulation of intracellular messengers or to sequestration of biologically active ANF bound to ‘clearance receptors’.

1. An experimental technique utilizing 'denervation diuresis' from one kidney with measurement of renin release from the contralateral innervated kidney was developed to study the sensitivity of renin secretion to volume depletion. 2. With urine excretion, release of renin increased progressively from the innervated kidney. The increase was significant at a sodium deficit of 0‐23 mole.kg‐1. At a sodium deficit of 0‐6 m‐mole.kg‐1 renin release had doubled. 3. Bilateral vagotomy did not alter this response. 4. Precise replacement of sodium loss with isotonic saline but without replacement of other urinary components returned renin release to control levels. 5. Slow haemorrhage causing a rate of volume and sodium loss equivalent to urinary drainage did not alter the rate of renin release. 6. With a single denervated kidney and contralateral nephrectomy, renin release fell progressively to minimal levels despite sodium deficits up to 2‐6 m‐mole.kg‐1. 7. It is concluded that renin secretion is sensitive to at most a 0‐5% change in body fluid volume and should be considered a primary response to volume depletion. The sensitivity of the response depends upon normal renal innervation but is not mediated via vascular volume receptors nor via receptors innervated by the vagus. 8. It is proposed that the extreme sensitivity of the renin‐secreting system in these experiments results from the combination of volume depletion and slight hypotonicity of extracellular fluid acting on the renal afferent arteriole without the mediation of the macula densa,

1. The effects of different energy substrates, of low temperature, of urea, and of ouabain and ethacrynic acid were studied on the rate of renin release from viable juxtaglomerular cells during superfusion of isolated rat glomeruli. 2. Neither lactate nor glutamate altered renin release rate from that observed using glucose as the sole energy substrate. Succinate 10 mM elevated release transiently but did not influence the release caused by reductions in osmolality through lowering sucrose concentration. 3. Peak renin release was more prolonged and returned more slowly to control following reductions in osmolality in phosphate‐Ringer than in bicarbonate‐Ringer. 4. At 37 degrees C, the peak of renin released induced by hypo‐osmolality was smaller and delayed, and returned earlier to control than at 30 degrees C. Reduction in temperature from 30 to 4 degrees C resulted in a 32‐fold increase in basal release rate. At 4 degrees C a 20 m‐osmole/kg reduction in tonicity caused an additional 2‐5‐fold increase in release rate. 6. Increasing superfusate osmolality with urea did not affect basal renin release but 100 mM urea suppressed the releasing effect of a 15 mM reduction in NaCl concentration. 7. Ouabain (10(‐4) M) caused a small (33 +/‐ 9%, P less than 0‐025) transient increase in renin release. Ethacrynic acid (10(‐3) M) provoked a progressive increase in release reaching 100 +/‐ 15% above control within 50 min. In the presence of both inhibitors the release provoked by hyposmolality was prolonged. 8. It is concluded that renin release in vitro is a function of actively regulated cell volume and it is proposed that a similar mechanism could underline both barorecptor and macula densa controls of renin secretion in vivo.

The rate of renin release from viable juxtaglomerular cells was studied during prolonged superfusion of isolated rat renal glomeruli with Ringer solutions of differing osmolarities. 2. Reduction in osmolarity from 305 to 285 m‐osmole/l. by lowering sucrose concentration caused renin release rate to double. A rise in osmolarity of 30 m‐osmole/l. by raising sucrose concentration halved release rate. 3. The response to osmolarity was graded. During the first 30 min following a 20 m‐osmole/l. decrease in osmolarity, 1‐57 +/‐ 0‐22% (S.E. of mean) of cellular renin content was released; three times this amount was released with a decrease of 50 m‐osmole/l. The effect persisted at lower release rates for 60‐90 min. 4. The juxtaglomerular cells were four to five times more sensitive to changes in osmolarity through sucrose than sodium chloride concentration. Changes in potassium chloride concentration (7‐57 mM) had little effect. 5. Sodium chloride had no direct ionic effect on renin release outside its osmotic properties. 6. The findings support a previous proposal that the rate of renin release in vitro relates directly to the volume of the juxtaglomerular cell. The hypothesis is developed that a similar mechanism may underlie renin secretion in vivo.

1. A method is described for studying renin release from superfused rat glomeruli following their rapid isolation by a magnetic iron‐oxide technique. 2. Microscopically selected glomeruli were free of tubular components. Some possessed vascular pole protrusions of up to 20 mum, unrelated to renin content. 3. Renin content of 102 batches, each of 400 glomeruli, was 1.34 plus or minus 0.08 times 10‐4 Goldblatt hog units per 100 glomeruli (plus or minus S.E. of mean). Different osmolarities (305, 355 and 400 m‐osmole/1.), sodium concentrations (110 and 135 mM) and buffer compositions of the preparation solution did not alter this value. Renin content per glomerulus in intact kidney was 100‐fold higher. 4. At 30 degrees C the contained juxtaglomerular cells released renin at consistent but decreasing rates over 4‐6 hr. Initial release rate in 110 mM sodium, 305 m‐osmole/1. solutions were 0.86 plus or minus 0.068 times 10‐6 units per 100 glomeruli per 30 min (plus or minus S.E. of mean, n = 42) or 0.546 plus or minus 0.046 percent of content per 30 min. In 135 mM sodium, 305 m‐osmole/1. solutions, release was 2.4‐fold higher (P less than 0.001) and remained elevated for at least 3 hr. When related to renin content per glomerulus resting release rate in vitro was higher by at most one order of magnitude than calculated in vivo values. 5. Release was augmented by gentle physical agitation of the glomeruli. 6. Release rate was inversely ralated to temperature. On reducing temperature from 30 degrees C, release increased 2.6‐fold at 20 degrees C and 6.7‐fold at 10 degrees C (P less than 0.001, n = 11). The response was reversible. 7. 3 mM sodium cyanide plus 3 mM sodium iodoacetate caused a variable release of renin associated with depletion of content within 4 hr. The response was progressive and reached a peak after 60 min. 8. Sensitivity of renin release to temperature and metabolic blockade indicates that energy is required for retention of renin by the cell. This, together with the release observed with increased sodium concentration at constant osmolarity, suggests a dependence of renin release upon the mechanism controlling the volume of the juxtaglomerular cell or its organelles.

1. The renal actions of ANP (average dose 30 ng kg‐1 min‐1 and glucagon (50 ng kg‐1 min‐1) were compared using fractional lithium reabsorption as the index of proximal reabsorption in groups of seven rats. Doses were chosen to cause similar increases in glomerular filtration rate (GFR). Time controls were included. 2. Glucagon raised GFR 32% and absolute proximal reabsorption (APR) 26% producing 81% effective proximal glomerulo‐tubular balance (GTB) which was not significantly different from the 100% expected for perfect GTB. ANP raised GFR 33% and APR 10% indicating only 30% effective GTB (P less than 0.01). This was a significantly different effect from glucagon (P less than 0.005). 3. Sodium output increased 10‐fold with ANP and 3‐fold with glucagon. Filtration fraction increased 33% (P less than 0.04) above the pre‐treatment value with ANP but was unchanged with glucagon. Plasma renin concentration was suppressed similarly by each hormone (46 and 36%, P less than 0.05, compared with pre‐treatment values). 4. Despite a change in peritubular physical factors favouring reabsorption, there was almost complete attenuation of the increase expected in APR with the ANP‐induced increase in GFR. In contrast, a similar change in GFR with glucagon resulted in an almost parallel increase in APR demonstrating maintenance of proximal GTB. 5. It is concluded that in the anaesthetized rat, ANP but not glucagon profoundly inhibits the increase in proximal reabsorption that normally follows an increase in filtered load. Such an action would contribute to the more potent natriuretic activity of ANP compared with glucagon.

1. Renal haemodynamic and tubular transport responses to low‐dose infusions (1 and 10 ng kg‐1 min‐1) of endothelin were investigated in anaesthetized rats. 2. Both doses caused transient increases in mean arterial blood pressure (17 +/‐ 5 mmHg, P < 0.05 at 1 ng kg‐1 min‐1) followed by sustained hypotension (‐14 +/‐ 5 mmHg, P < 0.05), reduced renal vascular resistance (‐42%, P < 0.05) and increased renal plasma flow (46%, P < 0.05). Glomerular filtration rate was unchanged. 3. Each dose caused profound diuresis and natriuresis. At 1 ng kg‐1 min‐1 urine flow rate and fractional water excretion increased 5‐fold and fractional sodium excretion 10‐fold. Fractional potassium excretion and solute‐free water clearance were unaltered. 4. End‐proximal fluid delivery estimated by lithium clearance doubled (P < 0.05) and fractional proximal and distal sodium reabsorption decreased 10‐20% (P < 0.05). Absolute proximal reabsorption also fell with the higher dose. 5. Hypotension and natriuresis persisted for 30 min after terminating infusions. Time‐control animals showed no changes in haemodynamics or renal tubular transport. 6. It is concluded that endothelin, at low concentrations, causes renal vasodilatation with concomitant natriuresis due to reduced sodium transport in proximal and distal nephron segments.

1. The influence of endogenous angiotensin II (AII) on renal haemodynamics and tubular function was examined by clearance and micropuncture methods in anaesthetized rats during AII receptor blockade with the non‐peptide antagonist DuP 753 (50 micrograms kg‐1 min‐1 i.v.). 2. Mean arterial pressure was reduced slightly (‐5 +/‐ 2 mmHg) while filtration fraction and glomerular filtration rate rose by 30% without changes in renal plasma flow (RPF) or renal vascular resistance (RVR). 3. Fractional proximal fluid reabsorption (calculated from lithium clearance) fell from 73 to 64% (P < 0.01) and fractional distal sodium reabsorption decreased from 98 to 94% (P < 0.01). 4. Urine flow rate more than doubled, sodium output increased 4‐fold and plasma renin concentration rose 8‐fold while potassium excretion remained unchanged. 5. Proximal tubular fluid reabsorption (Jv) as measured by shrinking split‐droplet micropuncture decreased by 21% (P < 0.01) during infusion of DuP 753 compared with 22.5% (P < 0.01) during converting enzyme inhibition by enalaprilat (MK422). 6. Responses to DuP 753 were similar to those previously documented with converting enzyme inhibitors except that DuP 753 failed to raise RPF. It is concluded that generation of intrarenal vasodilator paracrines has confounded conclusions about the renal action of converting enzyme inhibitors and we propose that in anaesthetized rats, endogenous angiotensin II (AII) has its major renal influences on glomerular filtration and proximal fluid reabsorption with little effect on renal vascular resistance.