Sodium Repletion Research Articles

Angiotensin and adrenal steroidogenesis: study of 21-hydroxylase-deficient congenital adrenal hyperplasia.

The effects of angiotensin have been studied in four adult patients with the simple virilizing form of congenital adrenal hyperplasia due to 21-hydroxylase deficiency. They were treated with hydrocortisone (25 mg/day) throughout this investigation. Plasma ACTH was normal in three cases, and androstenedione was normal in all cases. However, urinary pregnanetriol, plasma 17-hydroxyprogesterone (17 OHP), aldosterone, and renin activity was increased. The patients were then submitted to three protocols: sodium depletion (10 meq Na/day) for 5 days, sodium repletion (200 meq Na/day) for 5 days, and angiotensin infusion (sufficient to maintain a pressor response) for 60 min. Urinary pregnanetriol, plasma 17 OHP, and androstenedione levels increased in all patients after sodium depletion and decreased after sodium repletion. Plasma ACTH levels were not modified by changes in the sodium balance. Furthermore, angiotensin infusion increased aldosterone and 17 OHP plasma concentrations without any change in the plasma ACTH level. This study shows the direct action of angiotensin on adrenal steroidogenesis, at least in 21-hydroxylase deficiency. It confirms that even in the simple virilizing form, combined treatment with glucocorticoids and mineralocorticoids helps to normalize plasma 17 OHP levels.

Effect of prolonged infusions of angiotensin II on eight serum corticosteroids in man on different sodium diets.

The effects of long-term infusions of angiotensin II on serum progesterone, 17-OH-progesterone, deoxycorticosterone, corticosterone, 11-deoxycortisol, 18-OH-deoxycorticosterone, aldosterone and cortisol were studied in normal male subjects who were given normal or low sodium diets. While aldosterone levels exhibit the known marked increase during angiotensin II infusion, alterations of serum levels of the other steroids were absent or moderate. In the sodium replete state, an initial fall in 9 a.m. serum cortisol, 18-OH-deoxycorticosterone and corticosterone was followed by an increase of these steroids in the later phase of the infusion period. After Na+-restriction, however, a slight progressive increase of serum cortisol, 18-OH-deoxycorticosterone and corticosterone occurs after the onset of infusion. No changes of serum progesterone and 17-OH-progesterone are observed under sodium replete or low sodium conditions. These findings are tentatively explained by two mechanisms: 1) Angiotensin II has a "trophic" effect on the adrenal cortex, thus causing a progressive increase of secretion of corticosteroids in the normal sodium as well as in the low sodium state. 2) Angiotensin II may directly or indirectly inhibit ACTH secretion. This mechanism could be responsible for the initial fall of serum corticosteroids in the sodium replete state, while under low sodium conditions, this effect may be masked by the more pronounced mechanism.

The effect of chronic low-dose infusion of ACTH (1-24) on renin, renin-substrate, aldosterone and other corticosteroids in sodium replete and deplete man.

Abstract. Low-dose infusions of ACTH 1-24 (5 U/day) of 4 days duration were performed in 2 healthy young men on a normal sodium diet and in 2 on a low sodium diet, in order to study the mechanism of the transient effect of ACTH on aldosterone secretion described by other authors using larger doses of ACTH. Cortisol secretion was continuously stimulated by ACTH. Plasma aldosterone (P-Al) and its urinary metabolites increased during the first two days of infusion and returned to control or below control levels subsequently. Plasma renin activity (PRA) was also transiently stimulated by ACTH. Changes in PRA were not caused by changes in plasma renin substrate concentration. The correlation between PRA and P-Al (r = + 0.78; n = 52) was highly significant (P < 0.01). Plasma levels of deoxycorticosterone (DOC), 18-OH-DOC and corticosterone were also transiently stimulated in subjects on a normal sodium diet, while the stimulation was better maintained in those on a low sodium diet. The results suggest that the transient effect of low-dose ACTH infusion on aldosterone secretion may in part be mediated by changes in the renin-angiotensin-system. Changes in plasma levels of angiotensin II, which controls early and late steps in the mineralocorticoid biosynthetic pathway, may determine the extent to which chronically elevated ATCH levels stimulate the release of aldosterone and, perhaps, even the release of DOC and corticosterone. On the normal sodium diet, sodium retention and a slight fall in serum potassium levels towards the end of ACTH infusion may have contributed to the depression of aldosterone release.

DES-ASP 1] angiotensin II in the sheep: Blood levels and its effect on plasma renin concentration

The present study describes an improved method for measuring angiotensin III in arterial blood. This was accomplished by SE-sephadex column to separate angiotensin II from angiotensin III prior to radioimmunoassay. The arterial concentration of angiotensin III measured before and after 24 to 48 hours sodium depletion by acute cannulation of parotid gland was 12.4 ± 1.7 fmol/ml (SEM, n=7) and 49.8 ± 10.3 fmol/ml (SEM, n=7) respectively. The arterial concentration of Val 4-angiotensin III obtained from continuous infusion of Val 4-angiotensin III at rates of 24 and 48 nmol/h in sodium deficient sheep were 245 ± 32.5 fmol/ml (n=6) and 330 ± 11.4 fmol/ ml (n=7) respectively. The clearance rate of exogenous Val 4-angiotensin III in sodium deficient sheep after correction for endogenous level was calculated to be 140 ± 13.6 L/h (SEM, n=13). This was in the same order as Ile 5-angiotensin II and Ile 4-angiotensin III reported earlier in sodium replete sheep. Prolonged intravenous infusion of Val 4-angiotensin III at a rate of 48 nmol/h in sodium- deficient sheep suppressed plasma renin concentration to the same extent as equimolar infusions of angiotensin II. This suggests that angiotensin III may inhibit renin secretion by a similar mechanism to angiotensin II.

Hemodynamic, fluid, and electrolyte changes during sodium depletion in conscious dogs.

SummaryHemodynamic, fluid and electrolyte changes were studied during sodium depletion and repletion in six conscious dogs. Blood pressure (BP), plasma renin activity (PRA), heart rate (HR), cardiac output (CO), stroke volume (SV), and plasma volume (PV) were determined on 3 separate days in sodium replete conscious animals, similarly during sodium depletion, and again after sodium repletion. During sodium depletion, HR increased from 73 to 91 beats/min (P < 0.01). CO fell from 2.32 liters/min to 1.87 liters/min (P < 0.01). SV decreased from 32.6 ml to 21.7 ml (P < 0.01). Peripheral resistance (PR) increased from 41.5 to 49.2 mm Hg (liters/min)−1 (P < 0.01). BP was unchanged. PRA increased from 0.83 to 7.51 ng angiotensin I/ml/hr (P < 0.01). During the 8 days of sodium depletion, water intake was elevated on 6 days, urine volume was elevated on 5 days, and water balance was positive on 3 days. With sodium and volume repletion, all functions returned to control levels. The results demonstrate that sodium d...

Hypertension produced by sodium depletion and unilateral nephrectomy: a new experimental model.

Unilateral nephrectomy of sodium-restricted male Sprague-Dawley rats produced a sustained elevation in systolic blood pressure (SBP) that was reversed by sodium repletion. A chronic intraperitoneal infuson of SQ14,225 prevented the development of hypertension in sodium-deplete unilaterally nephrectomized rats. Sodium depletion of two-kidney rats increased SBP to a lesser extent, while unilateral nephrectomy of sodium replete animals had no effect. These results provide evidence for a new model of experimental hypertension in the rat and emphasize the importance of a renal component, as demonstrated by unilateral nephrectomy, in the maintenance of normal pressure-volume relationships.

Aldosterone response to angiotensin blockade in the conscious sodium-depleted rabbit.

SummaryTo evaluate the role of the renin-angiotensin system in the aldosterone response to sodium depletion in the conscious rabbit, angiotensin blockade was achieved with [Sar1, Ala8] angiotensin II and SQ 20881. After infusion of [Sar1, Ala8] angiotensin II (1 μg/kg/min) for 60 min into sodium-depleted animals, PAC was unchanged (33.3 ± 7.4 ng% compared with a control sodium-deplete value of 41.1 ± 8.2 ng%). When the dose was increased to 50 μg/kg/min for an additional 60 min, PAC fell to 15.4 ± 3.7 ng% (P < 0.0125), a value similar to the sodium replete value. In a second group of animals, SQ 20881 was given initially as a 7 mg/kg bolus and followed by an infusion of 60 μg/kg/min for 30 min; PAC fell from a sodium-deplete level of 86.6 ± 21.0 to 63.9 ± 18.2 ng% (P < 0.025). The infusion was extended to 60 min in five of the seven animals and PAC remained significantly reduced (63.3 ± 16.2 ng%, P < 0.01). These studies demonstrate that attenuation of the aldosterone response to sodium depletion occurred...

The effect of diet on echocardiographic left ventricular dimensions in normal man

The effect of dietary sodium and potassium on echocardiographic left ventricular dimensions was studied in normal subjects. In 10 subjects, left ventricular end diastolic volume was found to be 18.8% greater, and end systolic volume 17.1% higher with a 200 mEq sodium diet than on a 10 mEq sodium diet (P < 0.025). While receiving an ad libitum diet, the subjects were found to have an end diastolic volume of 107.9 ± 6.4 ml SE and an end systolic volume of 45.2 ± 2.7 ml SE. During sodium depletion, values fell to 101.3 ± 5.7 ml SE and 38.6 ± 2.9 ml SE, respectively, then on a high sodium diet rose to 120.3 ± 7.0 ml SE and 45.2 ± 2.7 ml SE, respectively. Heart rate fell during sodium repletion by 4.2% (P < 0.05) while mean arterial blood pressure, cardiac output and peripheral vascular resistance did not change significantly. In contrast, seven subjects consuming a diet containing 25 and 200 mEq potassium in sequence, the sodium intake remaining constant, did not display significant changes in cardiac dimension, heart rate, blood pressure, cardiac output, or vascular resistance. It is concluded that dietary sodium significantly effects the size of a nonfailing left ventricle, an effect that must be considered when single or sequential echocardiograms are interpreted.

Plasma active and inactive renin in the rabbit: effect of dietary sodium depletion and repletion.

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.

Sodium-Losing Nephropathy

AbstractWe studied prospectively 18 patients with sodium-losing nephropathy. In 12 patients (66.7 per cent) the sodium-losing nephropathy was owing to obstructions, challenging the hitherto existing concept that the most commoncause of the condition is pyelonephritis. The diagnosis of sodium-losing nephropathy is important in urological practice since sodium repletion in these cases shortens significantly the hospitalization and preoperative waiting time.

Prolonged pseudoaldosteronism induced by glycyrrhizin.

We describe the natural recovery from the aggravated hypertension, hypokalemia and suppression of the renin-aldosterone axis after the glycyrrhizin discontinuation in two mild hypertensive women aged 71 and 68 years, who had been administered 273 to 546 mg glycyrrhizin daily for 1.5 and 6 months, respectively, for the treatment of liver disease. About one month after the glycyrrhizin discontinuation, acceleration of hypertension, hypokalemia and suppression of the renin-aldosterone system still continued in both patients. At this stage, sodium restriction resulted in the normalization of blood pressure with weight loss and the subsequent sodium repletion produced a rapid increase in blood pressure to hypertensive levels observed before sodium restriction, with weight gain. Plasma renin activity and plasma aldosterone were low and did not respond to sodium restriction. Inappropriately excessive amounts of potassium were also excreted in the presence of hypokalemia. About one and a half months later, the improvements of aggravated hypertension, hypokalemia and suppressed renin-aldosterone system gradually occurred in both patients. Sodium restriction performed about three months later in case 2 no longer produced the changes in blood pressure and body weight. Plasma renin activity and plasma aldosterone responded subnormally to sodium restriction. These results demonstrate that both patients had a prolongation of the syndrome resembling primary aldosteronism except the low plasma aldosterone level about one month after the glycyrrhizin discontinuation. The possible mechanisms by which this prolongation was caused are discussed.

Renin response to upright posture in varying sodium balance in normal young Japanese men.

For the quantitative analysis of the effect of sodium balance on renin secretion, plasma renin activity (PRA) was measured in 9 healthy young males in the respective 3- or 4-day periods of sodium repletion, mild sodium restriction, moderate and severe sodium depletion. In the latter 2 periods, sodium balance was made negative by low salt diet and furosemide administration (120mg/day, p.o.) for 1 or 3 days. Blood samples for PRA determination were obtained at supine position (8:00 a.m.) and after 1-, 2-, and 4-hour's upright posture. PRA was also measured after furosemide stimulation (80mg, p.o.) plus 2-hour's upright posture in the period of sodium repletion.Change in the supine PRA was directly correlated with that in hematocrit (r=0.81) and inversely with that in body weight (r=-0.64). The PRA rose significantly from 1- to 2- and 4-hour's upright posture in the period of mild sodium restriction, whereas it reached the maximum level at 1-hour's upright posture and remained unchanged thereafter in either period of negative sodium balance. The upright PRA after furosemide stimulation in the period of sodium repletion was almost identical to 2- and 4-hour's upright PRA in the period of mild sodiom restriction, and less than 1-hour's upright PRA in either period of negative sodium balance.These data suggest that 1-hour's upright posture is enough to evaluate PRA when sodium balance is negative.

Catecholamines in Peripheral Venous Plasma in Patients on Chronic Haemodialysis

1. Concentrations of noradrenaline and adrenaline from peripheral venous plasma were measured after 60 min of supine rest in 55 patients on chronic haemodialysis (including six anephric patients) and in 18 normal subjects. In the patients, plasma catecholamine measurements were related to concurrent measurements of blood pressure, pulse rate, plasma renin activity, plasma angiotension II, blood volume and sulphate space. 2. Mean resting peripheral venous plasma noradrenaline concentration was higher by almost twofold, but mean resting plasma adrenaline concentration was lower, in the 49 non-nephrectomized patients than in the normal subjects. In the six anephric patients, resting peripheral venous plasma noradrenaline concentrations were similar to those of normal subjects. 3. Mean resting plasma noradrenaline concentrations in peripheral venous blood were similar in normotensive and hypertensive non-nephrectomized patients; mean plasma adrenaline concentration was higher in the hypertensive patients. A positive correlation was found between plasma adrenaline and plasma renin activity but not between plasma noradrenaline and plasma renin activity. 4. Resting concentrations of both catecholamines were positively correlated with resting pulse rate and inversely related to blood volume. 5. After renal transplantation resting peripheral venous plasma noradrenaline concentrations were normal in eight patients in whom high values had been recorded whilst on chronic haemodialysis. 6. In response to 40° of head-up tilt, plasma noradrenaline increased significantly in six non-nephrectomized patients, whether sodium replete or depleted, and the changes observed in both these states were similar to those of 14 normal subjects studied on a normal diet. 7. Diastolic blood pressure increased on standing in the majority (41/55) of patients: in only four patients was there a fall in diastolic pressure of more than 5 mmHg in the erect position and in two of these blood volumes were low. 8. The cause of increased peripheral plasma noradrenaline concentrations in haemodialysis patients is uncertain.

ALDOSTERONE, CORTICOSTERONE, CORTISOL. II-DEOXYCORTISOL AND II-DEOXYCORTICOSTERONE CONCENTRATIONS IN THE BLOOD OF CHRONICALLY CANNULATED OVINE FOETUSES: EFFECT OF ACTH

ABSTRACT Aldosterone, corticosterone, cortisol, 11-deoxycortisol and 11-deoxycorticosterone were measured, using a double isotope dilution derivative assay, in whole blood samples of ovine foetuses bearing chronic vascular cannulae. All values are quoted as mean ± standard error of mean. n = number of samples. Parturition occurred at 142–152 days. The concentration of aldosterone (ng/100 ml blood) was 8.7 ± 2.5 at 100–109 days, (n = 8), 4.4 ± 1.2 at 110–140 days (n = 32) and 11.5 ± 2.0 (n = 6) at 140 days until term. The value in unstressed, sodium replete pregnant sheep was 1.2±0.4 (n = 12). Neither corticosterone nor 11-deoxycortisol concentrations varied throughout gestation and were respectively 0.08 ± 0.02 and 0.03 ± 0.04 μg/100 ml blood in 56 samples. These values are essentially the same as those of pregnant, unstressed sheep. Total blood cortisol concentration was 0.10 ± 0.01 μg/100 ml in 38 samples from foetuses younger than 135 days, which is lower than the value for pregnant, unstressed sheep of 0.43 ± 0.07 (n = 34). Cortisol values rose after 135 days to reach 0.93 ± 0.3 (n = 7) after 140 days. The concentration of 11-deoxycorticosterone was 33.8 ± 8.0 ng/100 ml blood (n = 7) in the period 100–109 days, then decreased to 18.7 ± 4.4 (n = 45) from 110 days to term. The concentration in unstressed pregnant sheep was 26.3 ± 10 (n = 10) which is higher than non-pregnant sheep 2.33 ± 0.65 (n = 30). Infusions of ACTH (Synacthen®) 5 IU/h for 90 min had no consistent effect on the peripheral blood concentration of aldosterone, 11-deoxycorticosterone or 11-deoxycortisol at any stage, but elevated corticosterone values significantly (P &lt; 0.01) in all foetuses. Cortisol concentrations were significantly elevated (P &lt; 0.05) in foetuses of 135 days gestation or older.

Renal responses to angiotensin II and 1-sar-8-ala-aII in sodium replete and deplete dogs.

In order to elucidate the effects of angiotensin II on renal function, angiotensin II (AII; 1 ng/kg per min) and the AII antagonist 1-sar-8-ala-angiotensin II (AIIA; 200 ng/kg per min) were infused into the renal artery of anesthetized dogs (pentobarbital), on either a high (8 mmol/kg per day for seven days) or a low sodium intake (0.5 mmol/kg). In sodium replete dogs AII produced renal vasoconstriction with decreased RBF (-28%; P less than 0.001), but with less decrease of GFR (-14%; P less than 0.001), leading to an increase of FF (+19%, P less than 0.001), andantidiuresis (-39%, P less than 0.001); the antinatriuresis (-58%; P less than 0.001) exceeded the antidiuresis (P less than 0.001). delatRBF (-10%; P less than 0.001) was less pronounced (P less than 0.001) during AII in sodium deplete dogs, GFR remained unchanged, but FF increased to the same extent (+16%; P less than 0.05); diuresis and urinary electrolyte excretion were however not affected. AIIA did not affect RBF, GFR, FF, nor diuresis in sodium replete dogs suggesting that endogenous AII has no tonic influence on renal function in these conditions. In sodium deplete animals AIIA produced an 11% (P less than 0.001) increase of RBF, without changes of GFR; FF decreased by 12% (P less than 0.01), but diuresis, natriuresis and kaliuresis were not affected.

Prolonged Infusions of Ile5-Angiotensin-II in Sodium Replete and Deplete Man: Effects on Aldosterone, ACTH, Cortisol, Blood Pressure, and Electrolyte Balance*

Angiotensin II (Ile5) was infused for 72 h into 4 sodium replete (3 ng/kg/min) and 8 sodium deplete (3 or 6 ng/kg/min) healthy young men after appropriate control periods, and the effects on aldosterone secretion, plasma cortisol, ACTH, renin activity, plasma and urinary electrolytes, and blood pressure were assessed. Sustained contrived elevation of plasma angiotensin II levels in sodium replete subjects to the range of moderate sodium depletion led to a sustained increase in plasma and urinary aldosterone levels, which further and significantly increased between the 1st and 2nd days of angiotensin II infusion, when gross sodium retention during infusion was prevented. This additional increase may be explained as the expression of a "trophic" effect of angiotension II on the zona glomerulosa. In the sodium deplete state, the absolute increment of aldosterone secretion for a given elevation of angiotensin II levels diring infusion was larger than in sodium replete subjects. This confirms the conclusions from previous short-term angiotensin II infusion experiments that sodium deficiency sensitizes the zona glomerulosa against angiotensin II. The "trophic" effect of angiotensin II on the adrenal gland seems to be one mechanism by which the sensitization is brought about, but insufficient for its full explanation. Since plasma ACTH and cortisol, plasma sodium and potassium concentrations, and potassium blance did not change significantly across sodium depletion or angiotensin II infusion, the mechanism of sensitization awaits its full elucidation. The effect of angiotensin II on blood pressure was blunted by soidum depletion. The opposite shifts in sensitivity against angiotensin II of the zona glomerulosa and of resistance blood vessels with changes in the sodium state seem to be an effective and important means in the regulation of body sodium.

The effect of altered sodium balance upon renal vascular reactivity to angiotensin II and norepinephrine in the dog. Mechanism of variation in angiotensin responses.

The mechanism whereby the vasoconstrictor response to angiotensin II (AII) is influenced by sodium balance or disease is unclear. To explore this question, the renal vascular responses (RVR) to intrarenal injections of subpressor doses of AII and norepinephrine were studied in dogs with an electromagnetic flowmeter. Acute and chronic sodium depletion increased plasma renin activity (PRA) and blunted the RVR to AII, while acute sodium repletion and chronic sodium excess plus desoxycorticosterone acetate decreased PRA and enhanced the RVR to AII. The magnitude of the RVR to AII was inversely related to PRA. The RVR to norepinephrine was unaffected by sodium balance and was not related to PRA. Inhibition of the conversion of angiotensin I to AII by SQ 20,881 during sodium depletion lowered mean arterial blood pressure (MABP), increased renal blood flow (RBF), and enhanced the RVR to AII but not to norepinephrine. Administration of bradykinin to chronically sodium-depleted dogs also lowered the MABP and increased RBF but had no effect on the RVR to AII. SQ 20,881 had no effect on MABP, RBF, or the RVR to AII in the dogs with chronic sodium excess and desoxycorticosterone acetate. Administration of indomethacin to chronically sodium-depleted dogs lowered RBF but did not influence the RVR to AII. The results indicate that the RVR to AII is selectively influenced by sodium balance and that the magnitude of the response is inversely related to the availability of endogenous AII. The data did not suggest that the variations in the RVR to AII were because of direct effects of sodium on vascular contraction, changes in the number of vascular AII receptors, or the renal prostaglandins. The results are consistent with the hypothesis that the vasoconstrictor effect of AII in the renal vasculature is primarily dependent upon the degree to which the AII vascular receptors are occupied by endogenous hormone.

Effect of Angiotensin Converting Enzyme Inhibition on Blood Pressure, Plasma Renin Activity and Plasma Aldosterone in Essential Hypertension *

An angiotensin converting enzyme inhibitor was administered to 15 patients with essential hypertension after periods of sodium depletion and repletion, and the responses of blood pressure, plasma renin activity, and plasma aldosterone were recorded in the supine and erect position. After Na depletion the converting enzyme inhibitor induced significant fall of blood pressure in the supine position in all patients; in the erect position, 5 patients became hypotensive whereas the remaining exhibited increases in blood pressure to variable degree. After Na repletion, the converting enzyme inhibitor induced a lesser fall in blood pressure in 3 patients in the supine position, whereas in the erect position all patients exhibited increases in blood pressure. Plasma renin activity rose after injection of the inhibitor in all patients in both phases and was further stimulated by the upright posture. Plasma aldosterone declined after injection in both phases in the supine position. However, in the erect position al...

The effect of the converting enzyme inhibitor SQ 20.881 on kinins, renin-angiotensin-aldosterone and catecholamines in relation to blood pressure in hypertensive patients.

Nine sodium replete hypertensive patients with normal or high plasma renin activity (PRA) were given SQ 20.881, 1 mg/kg intravenously BP fell significantly within 20 min and reached its lowest level after 60 min. Blood kinins showed a minor but significant decrease after 60 and 105 min. Plasma angiotensin II was markedly reduced after 15 and 60 min. PRA was significantly increased after 15-105 min. Plasma aldosterone was reduced at 60 min in eight patients and slightly increased in one. Plasma noradrenaline increased after 15 min, whereas adrenaline decreased after 60 min. These results indicate that the reduction of BP following inhibition of converting enzyme by SQ 20.881, 1 mg/kg, is not related to reduced degradation of kinins but rather to decreased formation of angiotensin II. Angiotensin II appears to be of importance for the maintenance of BP in sodium replete hypertensive patients with normal or high PRA.

Effects of 1-sar-8-ala-angiotensin II on arterial pressure, renin and aldosterone in hypertension.

1-Sar-8-ala-angiotensin II did not change intra-arterial pressure in 25 sodium replete hypertensive patients, whilst the pressure changes were closely related to the plasma renin level during sodium depletion (r = -0.87; n = 32). The study indicates that arterial pressure is not dependent on angiotensin II in sodium replete patients and in sodium deplete subjects with low PRC, while it is angiotensin dependent during sodium depletion in the others. Plasma renin is unaffected in sodium replete subjects, but increases during saralasin in sodium deplete conditions. Saralasin stimulates aldosterone secretion only in sodium replete patients.