Circadian rhythms of serum renin activity and serum corticosterone, prolactin, and aldosterone concentrations in the male rat on normal and low-sodium diets

To investigate the control of aldosterone secretion, non-stress levels of serum aldosterone, corticosterone, and prolactin, and renin activity were determined at 4-h intervals during 24-h light-dark cycles in adult male rats on regular and low-sodium diets. Circadian rhythms of plasma aldosterone, prolactin, and corticosterone concentrations and of serum renin activity were demonstrated during a regular sodium diet. When the rats were on a low-sodium diet, a circadian rhythm of serum corticosterone and aldosterone concentration was observed, but there was no circadian variation in serum renin activity or in serum prolactin concentration. Serum aldosterone concentration correlated with serum corticosterone concentration (r = 0.48) and serum renin activity (r = 0.36) during a low-sodium diet. Serum prolactin concentration did not correlate with serum aldosterone concentration or serum osmolality. These data are compatible with a role for renin and ACTH, but not for prolactin, in the modulation of aldosterone secretion in the rat.     

The influence of dose and dose rate on the incidence of neoplastic disease in RFM mice after neutron irradiation

The effect of circadian rhythm and alterations in posture on plasma aldosterone concentration was studied in 13 patients with primary aldosteronism (six adenoma, five idiopathic hyperplasia, two carcinoma) to define the regulatory mechanism in each of these pathologic subtypes. Blood samples for aldosterone, cortisol, renin, and potassium concentrations were obtained every 4 h during prolonged recumbency (32 h) and upright posture (16 h). During recumbency, aldosterone and cortisol followed a normal circadian pattern in patients with adenoma and hyperplasia, with peak values at 0400-0800 h and the nadir at 1600-2400 h. Normalized aldosterone and cortisol values correlated significantly in both groups (adenoma r=+0.66, P less than 0.001; hyperplasia r=+0.42, P less than 0.01). With upright posture, aldosterone levels declined parallel to the normal circadian fall in cortisol in patients with adenoma (r=+0.68, P less than 0.001); whereas aldosterone levels increased in patients with hyperplasia parallel to small increments in renin (r=+0.65, P less than 0.001) and potassium (r=+0.64, P less than 0.001). During the administration of dexamethasone, aldosterone no longer correlated with cortisol in patients with adenoma but continued to correlate with renin during upright studies in patients with hyperplasia (r=+0.77, P less than 0.01). Aldosterone circadian rhythm was abnormal in patients with carcinoma and no effect of posture was noted. Unilateral adrenalectomy restored the normal postural relationship in four patients with adenoma. These studies suggest that aldosterone secretion is under continuous ACTH control regardless of posture in patients with adenoma, whereas persistent adrenal responsiveness to small increments in renin and/or potassium mediate the postural increase in plasma aldosterone in patients with hyperplasia. True adrenal autonomy occurs only in patients with adrenal carcinoma and when ACTH is suppressed in those with adenoma.     

Relationship between plasma aldosterone concentration and plasma potassium in patients with essential hypertension during alprenolol treatment

Plasma aldosterone concentration (PAC), plasma renin concentration (PRC), plasma potassium, plasma sodium and blood pressure (BP) have been measured in 22 patients with essential hypertension before and after treatment for one month with alprenolol. PAC, PRC and BP decreased and plasma potassium increased significantly during treatment. Plasma sodium, however, was unchanged. Changes in PAC were inversely correlated to changes in plasma potassium. No relationship could be demonstrated between PAC and plasma sodium. Mean BP was inversely correlated to PAC during alprenolol treatment, but bot before treatment. No relationship was found between changes in BP and changes in PRC. The results suggest that plasma potassium is an important regulatory factor for aldosterone secretion during alprenolol treatment. Other factors, however, must have a modulating influence and since the renin- angiotensin system is not suppressed to very low values, this system is possibly the most important of these factors. It is suggested that aldosterone secretion is not of primary importance in BP regulation during alprenolol treatment.     

Effects of coenzyme Q on plasma aldosterone concentrations in dogs (author's transl)

The renin-angiotensin system, potassium and adrenocorticotropin (ACTH) are well known as control mechanism for aldosterone secretion. However, the precise mechanism of these factors for aldosterone secretion remain still unclear. Several interesting evidences related to the effects of Coenzyme Q on the secretion and biosynthesis of aldosterone have been demonstrated. Biochemical action of Coenzyme Q is generally accepted as a component of the electron transfer process of respiration in mitochondria. Fabre et al demonstrated that significant reduction of plasma aldosterone concentration in adrenal venous by the Coenzyme Q infusion. Weinstein et al observed that urine sodium excretion decreased after infusion of Coenzyme Q into renal artery. Kumagai et al suggested that Coenzyme Q inhibited the activity of 18-hydroxylase in the adrenal cortex. The present study was designed to evaluate the effects of Coenzyme Q on the secretion of aldosterone. Method: 24 cases of male among el and beagle dogs were subdivided into 4 groups. 1st group were administered intravenous infusion of Coenzyme Q, 2nd group were orally administered Coenzyme Q for 7 weeks, 3rd group were administered simultaneous infusion of Coenzyme Q and angiotensin II and 4th group were administered furosemide orally under the condition of continuous Coenzyme Q administration. Then, plasma concentrations of aldosterone, 11-OHCS and angiotensin I were determined during the time course. Results and Discussions: Plasma aldosterone concentration was significantly increased after intravenous infusion of angiotensin II and decreased 45 minutes after the beginning of infusion. However, the concentration still remained higher than control level. By the simultaneous infusion of Coenzyme Q with angiotensin II, the decreased concentration again increased significantly. It seems that above mentioned results suggest possibility that Coenzyme Q potentiate the action of angiotensin II on aldosterone secretion. By the intravenous infusion of Coenzyme Q, plasma aldosterone concentration increased significantly and concentrations of plasma 11-OHCS and angiotensin I did not affected. This result suggests that Coenzyme Q may stimulate aldosterone secretion from adrenal cortex without increase of ACTH and renin-angiotensin. 4 hours after the oral administration of Coenzyme Q, plasma aldosterone concentration was increased significantly. Na/K in 24 hours' excreta was decreased by Coenzyme Q administration. The decrease of Na/K in excreta may be reflection of the increase of aldosterone secretion. Although, plasma aldosterone concentration increased for the short duration by the Coenzyme Q, it decreased gradually and returned to the control level after 7 days under the condition of continuous oral administration. By the oral administration of furosemide under prolonged Coenzyme Q administration plasma aldosterone concentration increased significantly and remained higher than that of control.     

Ethanol-induced changes in plasma proteins, angiotensin II, and salt appetite in rats.

Sodium depletion in rats elicits a sodium appetite that results from a cerebral action of angiotensin II (ANG II) and aldosterone. Alcohol also activates the renin-angiotensin system, but the mechanism is poorly understood and not related to sodium excretion. In this study, 2.5 g/kg intraperitoneal/ly (ip) ethanol produced a 20% decline in plasma volume and plasma protein concentration 1–2 hrs and elicited salt appetite beginning in 3–4 hrs. Blockade of ANG II synthesis in the brain and periphery with the angiotensin-converting enzyme inhibitor captopril eliminated the thirst and salt appetite. Peripheral captopril alone enhanced fluid intake, which indicated that alcohol elevated renin secretion. Ethanol-induced suppression of hepatic plasma protein secretion and the consequent fall in plasma colloid osmotic pressure apparently resulted in hypovolemia and renin secretion, which then produced thirst and salt appetite through an action of ANG II on the brain. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effectiveness of the aldosterone-sodium and -potassium feedback control system

This study was conducted to determine the quantitative importance of the aldosterone feedback mechanism in controlling each one of three major factors that have often been associated with aldosterone, namely, extracellular fluid sodium concentration, extracellular fluid potassium concentration, and extracellular fluid volume. To do this, the ability of the body to control these three factors in the face of marked changes in daily sodium or potassium intake was studied under two conditions: 1) in the normal dog, and 2) in the dog in which the aldosterone feedback mechanism was prevented from functioning by removing the adrenal glands and then providing a continuous fixed level of supportive aldosterone and glucocorticoids during the low and high electrolyte intake periods. Under these conditions, removal of feedback control of aldosterone secretion decreased the effectiveness of plasma potassium control by nearly fivefold (39% vs. 8% change in plasma potassium concentration), fluid volume by sixfold (12% vs. 2% change in sodium space) and had no effect on control of plasma sodium concentration (2% change with and without feedback control of aldosterone secretion.)     

Regulation of 18-oxocortisol and 18-hydroxycortisol by the renin-angiotensin system and ACTH in man

Based on urinary excretion studies the secretion of the cortisol derivatives, 18-oxocortisol and 18-hydroxycortisol are believed to be regulated by ACTH and to a lesser degree by the renin-angiotensin system. Plasma concentrations of 18-oxocortisol and 18-hydroxycortisol were measured during the simultaneous activation of the renin-angiotensin system and inhibition of ACTH secretion. Five healthy male subjects consuming a sodium diet ad libitum were studied. Blood was drawn at 0800 h after 1 h in the supine position. In the first set of experiments, the subjects remained in the supine position from 0800 to 1000 h with or without the oral administration of 2 mg dexamethasone at 0800 h. In the second set of experiments the subjects were placed in the upright position after drawing the 0800 h sample. The subjects were studied with and without dexamethasone administered at 0800 h. Blood was drawn again at 1000 h. Plasma levels of 18-oxocortisol, 18-hydroxycortisol, ACTH, plasma renin activity (PRA), cortisol, aldosterone and 18-hydroxycorticosterone were measured by radioimmunoassay. None of these parameters changed during the 2 h in the supine position. 18-Oxocortisol, 18-hydroxycortisol, aldosterone, 18-hydroxycorticosterone and PRA increased, but ACTH and cortisol did not change when the subjects were placed in the upright position. After dexamethasone administration, 18-oxocortisol, 18-hydroxycortisol, cortisol, aldosterone and 18-hydroxycorticosterone decreased in the supine position and no increase occurred in 18-oxocortisol, 18-hydroxycortisol and 18-hydroxycorticosterone in the upright position. PRA and aldosterone increased and ACTH and cortisol decreased in these subjects. 18-Oxocortisol and 18-hydroxycortisol were more dependent on ACTH regulation and less on the renin-angiotensin system than aldosterone.     

Effect of administered potassium on the renin-aldosterone axis in young blacks compared with whites

BACKGROUND: We had observed previously that the aldosterone excretion rate and plasma aldosterone concentration were lower for black children than they were for white children. We did not know whether this was secondary to a lower intake of potassium or to suppression of the renin-angiotensin system in blacks. OBJECTIVE: To test the hypothesis that the secretion of aldosterone in response to potassium would be different in blacks than in a control group of whites. DESIGN: Black and white subjects were selected on the basis of their having aldosterone excretion rates that were in the lowest quartile for the entire original cohort. Since the blacks typically had lower aldosterone excretion rates than did the whites, the black participants were represented primarily by those with average rates of aldosterone production among blacks, whereas the whites were represented by those with the lowest aldosterone production rates among whites. The protocol consisted of a placebo-controlled, randomized cross-over study design. METHODS: Twelve blacks and 12 whites, aged 14.1 +/- 1.6 (mean +/- SD) and 15.4 +/- 2.1 years, respectively, were allocated randomly to double-blind treatment either with placebo or with 40 mmol/day potassium chloride for 7 days and then the alternate treatment Measurements of the plasma renin activity (PRA), plasma aldosterone concentration, and urinary aldosterone excretion were performed in an inpatient research unit at the end of the treatment. The blood pressure was monitored for 24 h. RESULTS: Treatment with potassium increased the plasma aldosterone concentration (P = 0.0006) and the urinary excretion of aldosterone (P = 0.0002) significantly both for blacks and for whites. There was no significant racial difference in the response to potassium. The PRA was overall 1.605-fold lower in the blacks than it was in the whites (P = 0.0124). The lowest PRA levels, such as those in the blacks when they were supine, tended to be increased with the potassium treatment. The blood pressure did not change significantly with the potassium supplement for either racial group. CONCLUSIONS: After we had supplemented the intake of potassium, aldosterone production increased in the blacks and in the control group of whites to the same extent The potassium treatment appeared to increase lower PRA levels. A lower intake of potassium could at least partially account for the suppression of the renin-aldosterone system in blacks.     

Variable effects of cardiomyoplasty on left ventricular function

Renin-angiotensin system promotes sodium and chloride retention, participates in the defense response to hypovolemia and, in congestive heart failure, contributes to edema formation and progression of the disease. We investigated whether ACE-inhibitors interfere with the action of the renin-angiotensin system on the nephron, and therefore with water and urinary electrolytes excretion. The interaction among renin-angiotensin system, diuretic treatment and urinary electrolytes was evaluated both during chronic treatment and in response to acute renin-angiotensin system activation as that observed after extracorporeal ultrafiltration-induced transient hypovolemia. Plasma renin activity and aldosterone, body fluid balance and urinary sodium, chloride and potassium concentrations were evaluated in 30 patients with congestive heart failure in NYHA II-III functional class, grouped according to whether long-term therapy did not include (Group I, n = 15) or included (Group II, n = 18) ACE-inhibitors. All parameters were evaluated at baseline and after a single session of extracorporeal ultrafiltration. At baseline, urinary output and urinary sodium and chloride concentrations were similar in the two groups, while urinary potassium concentration was lower in patients assuming ACE-inhibitors (Group II). Plasma renin activity was higher and aldosterone was lower in Group II than in Group I. After removal of similar amounts of plasma water by extracorporeal ultrafiltration, body weight decreased in both groups but the decrease was maintained in the following days only in Group II patients. A transient reduction (48 hours) of both plasma volume and urinary output was observed after ultrafiltration in both groups. Despite plasma renin activity and aldosterone increase, urinary electrolytes response to ultrafiltration was different in the two groups: sodium and chloride were reduced, and potassium did not change in Group 1 while, in Group II, sodium and chloride did not change and potassium excretion was significantly increased. In conclusion, chronic treatment with ACE-inhibitors does not enhance the excretion of sodium in congestive heart failure but just mitigates potassium loss. The role of these drugs becomes particularly relevant during acute renin-angiotensin system activation due to hypovolemia; in this setting ACE-inhibitors counteract sodium and chloride retention resulting in a potential hazard due to interference with the defence mechanisms toward hypovolemia, and an amplification of extracorporeal ultrafiltration efficacy by preventing edema recovery after its mechanical removal.     

The renin-angiotensin-aldosterone system in mother and fetus at term

Plasma renin activity, renin substrate, angiotensin II, aldosterone and cortisol were measured concurrently and renin concentration calculated in plasma from mothers during labor and delivery, from cord and from newborn infants. The renin-angiotensin-aldosterone system was found strongly stimulated in both mother and fetus. The high values of plasma renin activity in fetus were due exclusively to the high renin concentrations the substrate concentration being normal. In the mother, however, the markedly elevated renin substrate resulted in a doubling of relative values of renin activity compared to renin concentration. Therefore gradients of renin and renin substrate across the placenta are established, but the resulting renin activity is similar on both sides and the levels of generated angiotensin II are also nearly indentical with a good correlation between these last parameters. Aldosterone is as elevated in mother as in fetus whereas cortisol, due to its binding to transcortin, is twice as high in mother as in fetus. No correlation was found between renin activity or concentration of angiotensin II and aldosterone or cortisol indicating that other factors controlling aldosterone are involved.     

Hypertension treatable with glucocorticoids: report of a case

Lately, a series of hypertensive syndromes of unknown etiology that respond to new forms of therapy, have been described. One of these is glucocorticoid remediable hypertension, that evolves with suppressed plasma renin activity and normal or high serum aldosterone levels, that lead to an aldosterone/plasma renin activity ratio over 30. We report a 45 years old woman with a severe hypertension, despite the use of antihypertensive medications. She had a plasma renin activity of less than 0.3 ng/ml/h, normal serum aldosterone levels (10 ng/ml) and thus a high aldosterone/plasma renin activity ratio. She had normal serum potassium and sodium levels. Due to the bad results of conventional antihypertensive medications, a treatment with dexamethasone was started, that normalized blood pressure and allowed to discontinue other antihypertensive medications. This type of hypertension must be sought since non conventional treatments could be used for refractory hypertensive syndromes.     

A prospective study of omeprazole suspension to prevent clinically significant gastrointestinal bleeding from stress ulcers in mechanically ventilated trauma patients

We recently reported that administration of Nomega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) production, activates the vascular and cardiac renin-angiotensin systems and causes vascular thickening and myocardial hypertrophy in rats with perivascular and myocardial fibrosis. It has been reported that aldosterone may contribute to the development of cardiac fibrosis, but it is not known whether inhibition of NO synthesis affects angiotensin II (Ang II) receptor gene expression and aldosterone secretion. The aim of this study was to investigate the effect of NO inhibition on the expression of Ang II receptors in the adrenal gland and on aldosterone secretion in rats. Wistar King A rats received normal water, L-NAME alone (1 mg/mL in the drinking water), or L-NAME and the alpha1-adrenergic receptor blocker bunazosin (0.1 mg/mL in the drinking water) for 1 week. After 1 week of treatment with L-NAME, systolic blood pressure, plasma aldosterone concentration (PAC), and mRNA level and number of Ang II type 1 receptor (AT1-R) were increased. Plasma renin activity, serum angiotensin-converting enzyme activity, and the number of AT2-R were unchanged. Although addition of bunazosin to L-NAME restored systolic blood pressure to the control level, PAC and AT1-R numbers remained significantly higher than those of control level. These results suggest that the increased AT1-R number and PAC induced by the inhibition of NO synthesis were independent of blood pressure and systemic renin-angiotensin system. Therefore, hypertension and myocardial fibrosis induced by NO blockade may be due in part to an elevation of PAC caused by increased AT1-R in the adrenal gland.     

Differences between supine and sitting Frank-lead electrocardiograms

In babies ranging in age from 1 to 25 weeks and in children between 1 and 14 years, plasma renin activity and urinary aldosterone activity were determined in relation to urinary sodium excretion. A reciprocal correlation was found demonstrating that the hyperactivity of the renin-angiotensin-aldosterone system is stimulated in infants by a low sodium intake. A second stimulus was observed in the influence of the hypothalamo-neurohypophyseal system, when the plasma renin activity was suppressed by administration of antidiuretic hormone and sodium excretion increased due to a decreased aldosterone activity. Our study suggests that there exists a feedback between the renin-angiotensin-aldosterone system and ADH release and that this feedback plays an important role in the regulation of water and electrolyte balance in the young infant.     

Effects of varying sodium intake on blood pressure and renin-angiotensin system in subtotally nephrectomized rats

In rats in which the renal mass had been reduced by 70 per cent, the effects of varying sodium intake on blood pressure, serum electrolytes, renin-angiotensin system, and some other parameters that were modified simultaneously were studied. Within 4 weeks, a high sodium diet (750 mEa. per kilogram) resulted in marked hypertension, whereas a standard sodium diet (150 mEq. per kilogram) elevated the blood pressure only slightly. A low sodium diet (less than 0.2 mEq. per kilogram) prevented the rise in blood pressure. In the hypertensive group, the hematocrit values were markedly decreased, indicating the expansion of extracellular and intravascular spaces. The compensatory renal hypertrophy was accelerated by the high sodium diet and retarded during restriction. During low sodium intake, the serum concentration of sodium was diminished and that of potassium elevated. During the high sodium diet, the sodium concentration was unchanged, but the potassium concentration was decreased. Subtotal nephrectomy diminished the plasma angiotensin II concentration, and the renin content of the kidney remnant was lower than that of the kidneys from control animals. Sodium restriction stimulated the renin angiotensin system markedly, whereas high sodium intake suppressed it. After subtotal nephrectomy, elevation of blood pressure, renal hypertrophy, and suppression of the renin-angiotensin system are closely related to sodium intake.     

Effect of sodium restriction and angiotensin II infusion in Bartter's syndrome

Five patients with Bartter's syndrome were investigated. Sodium restriction (less than 10 mEq/day for at least 5 days) showed a renal sodium wastage in only two patients (I and II) in spite of increased aldosterone secretion rate (from 151-427 to 680-842 mug/day). The effect of angiotensin II (A II) 80ng/kg/min for 30-180 min, on plasma renin activity (PRA), plasma aldosterone, and urinary sodium excretion was compared with the effect of a previous infusion of 5% dextrose given at the same rate, 0.5 ml/min for 1 hr. A II infusion resulted in increased plasma aldosterone levels: from 236-330 pg/ml to 800-881 pg/ml in 30 min. This increase was also observed in patient II (from 139 to 600 pg/ml). PRA was decreased by A II infusion (from 1,142-2,462 to 121-1,625 ng/liter/min). In patient IV, this decrease in PRA was also observed when he was on a salt-restricted diet (from 1,934 to 370 ng/liter/min); but the minimal PRA was still higher (370 ng/liter/min) than with a normal diet (121 ng/liter/min). In no case could normal PRA level be obtained. A II infusion induced an increase in urinary sodium excretion only in the two patients with renal sodium wastage (from 80-90 to 265-230 muEq/min in 30 min). Urinary sodium excretion decreased in the other patients from (37.5-213 to 4.30-46 muEq/min) and fractional sodium excretion was reduced in patient V (from 0.56% to 0.45% at 30 min and to 0.29% at 120 min). No significant change with A II infusion was observed in patient IV when he was on a sodium-restricted diet (from 1 to 2.5 muEq/min in 30 min). Urinary potassium excretion was similar to sodium excretion. No change was observed in plasma potassium and sodium.     

Aldosterone and renin in liver cirrhosis with ascites

Supine plasma aldosterone and plasma renin activity were determined in patients with cirrhosis of the liver and ascites (n = 10). Most of the patients initially showed an increase in plasma aldosterone and plasma renin activity. However, values within the normal range were observed (plasma aldosterone, n = 3; plasma renin activity, n = 4). In the ascitic fluid renin activity could not be detected, whereas aldosterone concentrations correlated significantly with the respective plasma levels (r = 0.8, p less than 0.01). During therapy with spironolactone alone (n =2) or in combination with furosemide (n = 4), diuresis and natriuresis showed no correlation with changes in plasma aldosterone and/or plasma renin activity. Our results suggest that other factors than renin and aldosterone secretion may be important in the formation of ascites in patients with cirrhosis of the liver. In addition, the inverse correlation between mean arterial blood pressure and plasma renin activity (r = -0.65, p less than 0.05) found in our patients supports the assumption that the increase in renin secretion is probably induced by changes in (renal) hemodynamics.     

Morphogenesis of the lateral nasal wall from 6 to 36 weeks

Salt intake, and the sensitivity of blood pressure (BP) to excessive salt intake is thought to contribute to the pathogenesis of essential hypertension in some patients. This study was designed to ascertain whether salt sensitivity of BP is a determinant of BP and renal vascular responsiveness to angiotensin converting enzyme (ACE) inhibition. In 24 patients with essential hypertension, ranging in age from 30 to 68 years, renin status, renal hemodynamics, and sensitivity of BP to steady state changes in salt intake were assessed. Twenty-four hour ambulatory BP monitoring (ABPM) was employed to measure baseline BP and BP response to 4 weeks' treatment with benazepril at 20 or 40 mg/day. Benazepril induced a highly-significant reduction in BP (P < .001) and increase in renal plasma flow (530 +/- 17 to 580 +/- 19 mL/min/1.73 m2; P < .001). Systolic BP fell from 143 +/- 2 to 129 +/- 2 mm Hg (P < .001), and diastolic BP fell from 91 +/- 1.6 to 80 +/- 2 mm Hg (P < .001). The magnitude of the BP and renal vascular response to ACE inhibition was not influenced by the sensitivity of BP to salt intake. In a multivariate analysis neither body mass index nor age influenced the BP response to ACE inhibition or the relationships between salt intake and a BP response to ACE inhibition. We conclude that the factors that influence sensitivity of BP to salt intake do not influence the systemic or renal hemodynamic response to ACE inhibition.     

Torsemide inhibits aldosterone secretion in vitro

Torsemide inhibited aldosterone secretion by adrenal cells from rats, cows, and guinea pigs stimulated in vitro by potassium, angiotensin, dibutyryl cyclic AMP, ACTH, or corticosterone. Inhibitory concentrations for adrenal cells (micromolar) were comparable with those reported to inhibit ion transport in isolated renal tubules. Inhibition of aldosterone secretion could reduce kaliuresis, and that may explain why torsemide causes less kaliuresis than other diuretics.     

Aldosterone secretion during high sodium cerebrospinal fluid perfusion of the brain ventricles

Conscious sheep with permanent indwelling cannulae in the lateral ventricles and the cisterna magna were Na depleted and then perfused for 9 h with an artificial CSF solution. There were 3 experimental groups: Group I (n=5) received perfusion with aritifical CSF containing NA 170 MEq./1, Group II (n=7) received perfusion with artificial CSF containing Na 145 mEq./1, Group III (n=7) received no perfusion. In Group I the blood aldosterone level fell from 26.4 +/- 7.4 to 8.6 +/- 2.3 ng/100 ml by 9 h after perfusion. There was no significant change in plasma [Na] or [K], blood angiotensin II or plasma renin concentration. Blood cortisol and corticosterone levels rose. There was also a fall in post-perfusion. Group III showed no significant change in blood aldosterone concentration. Multivariate statistical analysis showed that the fall in aldosterone levels during 170 mEq./l Na perfusion could not be accounted for by changes, either alone or together, of ACTH as evidenced by alteration in blood cortisol or corticosterone, or by change of plasma [Na], [K] or renin concentrations. This data supports the hypothesis of an additional factor which may be of CNS origin being involved in the control of aldosterone secretion.