Renal effects of the acute inhibition of angiotensin-converting enzyme. I. 2) Studies during moderate potassium depletion]

We have investigated the relative roles of angiotensin II on the renal function and urinary excretion of some prostanoids in healthy women submitted to different conditions of potassium balance. To this aim we have evaluated the effects of an acute inhibition of angiotensin converting enzyme by enalapril (E). The renal function was explored by clearance (cl.) method during induced hypotonic polyuria (oral water load followed by 5% dextrose solution infusion). During 60 min cl. period the urinary PGE2, 6-keto-PGF1 alpha and TxB2 were determined by RIA method. Each subject received paired studies, in absence and presence of E (10 mg administered per os 1 hour before the water load). Basal values of plasma renin activity (PRA) and urinary aldosterone (excreted during the 24 hours before the water load) were also determined by RIA method. This study protocol was applied in normal potassium balance (n = 6) and induced moderate potassium depletion (n = 6). This paper concerns the group in potassium depletion in both absence (D4) and presence of E (D4.E). Potassium depletion was induced by adaptation to a normal sodium (150 mmol/d) and low potassium (< or = 10 mmol/d) dietary intake combined to natriuretic treatment. The water and NaCl net losses were restored by 0.9% NaCl solution infusion. The cumulative potassium deficit achieved at the end of the depletive treatment was 214 +/- 54 mmol. This treatment induced significant decrease in basal plasma potassium concentration and increase in PRA without affecting urinary aldosterone and plasma sodium concentration.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of bromocriptine on the control of plasma aldosterone diurnal variation in normal supine man.

In order to investigate the role of prolactin in the control of the circadian rhythm of plasma aldosterone (PA), plasma renin activity (PRA), cortisol (PC), aldosterone and prolactin (PRL) levels were determined in samples at 4-hour intervals from 5 normal supine men over a period of 24 h under basal conditions and subsequently over a period of 24 h during suppression of prolactin release by bromocriptine (CB-154). After suppression of prolactin, statistically signific1nt circadian rhythms in PC and PA have been detected with a moderate decrease of PA concentration, while the PC level remained unalterated. PRA rhythmicity persisted with a significant shift of acrophase and remarkable reduction of plasma levels. Moreover, during CB administration a significant correlation was obtained between PA and PC, while no correlation was detected between PA and PRA. These data are consistent with the following concepts: (a) the prolactin does not play a significant role in the regulation of circadian rhythm and concentration of plasma aldosterone in normal supine men, and (b) bromocriptine induces a remarkable reduction of PRA and a variable decrease in plasma aldosterone, but it does not influence the secretion of cortisol in normal subjects.     

Evidence for a cold-induced aldosterone stimulation in the rat

This study was undertaken to determine the secretion of aldosterone by male Long-Evans rats acclimated for six weeks to moderate cold (15 C), in comparison with rats maintained at thermo-neutral temperature (28 C). The following determinations were made: corticosteroids in plasma and adrenals, PRA, and hydromineral balance. Cold acclimation highly increased the plasma and adrenal levels of aldosterone and corticosterone. The cold stimulation of aldosterone was induced neither by the renin-angiotensin system, nor by alterations of hydromineral balance: PRA, plasma sodium and potassium concentrations, blood hematocrit, and hydromineral balance at 15 C and 28 C did not differ. Moreover this stimulation was induced neither by ACTH, nor by any other hypophyseal factors, since plasma aldosterone levels remained high in hypophysectomized rats. This study provides evidence of an aldosterone stimulation which appeared during moderate cold acclimation; the origin of this stimulation must be investigated.     

Effect of hypoxemia on the renin-angiotensin-aldosterone system in humans

Hypoxemia was induced in five subjects older than 40 (group 1) and five younger than 35 yr (group 2) on normal and low-salt diets by having the subjects breathe hypoxic gas. The fractional inspired O2 of the hypoxic gas was regulated so that group 1 hemoglobin saturations fell to 90% for 1 h. Group 2 subjects had desaturation to 90% for 1 h followed by desaturation to 80% for a 2nd h. Plasma renin activity (PRA), angiotensin-converting enzyme activity (ACE), and plasma cortisol levels did not change during hypoxemia. Plasma aldosterone levels fell in both groups during the 1st h of hypoxemia. Decreases were greatest during salt restriction and were significant (P less than 0.01) for the combined groups. Plasma aldosterone levels plateaued during the 2nd h of more severe hypoxemia in group 2. Hepatic blood flow, measured by indocyanine green clearance, and the adrenal response to exogenous adrenocorticotropic hormone, measured by changes in plasma cortisol and aldosterone, were not changed by hypoxemia in group 2 subjects. These results indicate that plasma aldosterone falls during hypoxemia despite unchanged PRA, ACE, hepatic blood flow, and adrenal function.     

Direct measurement of immunoreactive renin during changes of posture in man.

For several years, it has been possible to determine renin by a direct RIA. In the present study, plasma active renin concentration (PRC) was related to plasma renin activity (PRA) and aldosterone as a function of a standardized posture test. Using PRC, our target was to define the shortest necessary test duration. The three parameters were examined in 10 healthy male subjects (22-34 years old). Salt balance was determined in 24-hour urine, and plasma potassium and sodium were measured. Volunteers were hospitalized for 1 night, and at 8 a.m. the next morning they were subjected to the following postural changes: 3 h active orthostasis and 3 h recumbency. Frequent blood samples were taken. Orthostasis induced a significant rise in PRC, PRA and aldosterone already after 15 min. PRC and PRA reached a maximum level after 90 min of orthostasis and remained relatively stable, while aldosterone reached its highest level already after 30 min and then gradually decreased. Significant correlations were found between PRA and PRC (p < 0.001), between PRC and aldosterone (p < 0.001), and between PRA and aldosterone (p < 0.001). The PRC/PRA ratio changed during the course of the test, especially in supine subjects. When subjects returned to the supine position, all the parameters measured began a continual decrease. There were no significant changes in serum potassium and sodium levels throughout the duration of the test.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of prolonged ACTH stimulation on adrenal renin and aldosterone

Changes in adrenal renin, which have been regarded as mediator of aldosterone secretion in the adrenal gland, following prolonged ACTH treatment were investigated in male Wistar rats. After 2 days of daily sc injection of ACTH (Cortrosyn-Zinc, 50 micrograms/day), parallel increases in adrenal renin and aldosterone, and plasma aldosterone (PA) were induced. The plasma renin activity (PRA) was slightly but not significantly decreased. Prolonged treatment with ACTH for 8 days increased the adrenal renin, causing a marked reduction in the adrenal aldosterone concentration. The degree of decrease in the PRA was again not significant and similar to that after 2 days of ACTH treatment. Contrary to previout reports which have indicated participation of adrenal renin in the regulation of aldosterone secretion in the adrenal gland, the present results showed reciprocal changes in adrenal renin and aldosterone after prolonged treatment with ACTH. The present findings suggest a complicated relation between adrenal renin and aldosterone secretion in the adrenal gland.     

Brain-derived adrenomedullin controls blood volume through the regulation of arginine vasopressin production and release

Central nervous system-derived adrenomedullin (AM) has been shown to be a physiological regulator of thirst. Administration of AM into the lateral ventricle of the brain attenuated water intake, whereas a decrease in endogenous AM, induced by an AM-specific ribozyme, led to exaggerated water intake. We hypothesized that central AM may control fluid homeostasis, in part by regulating plasma arginine vasopressin (AVP) levels. To test this hypothesis, AM or a ribozyme specific to AM was administered intracerebroventricularly, and alterations in plasma AVP concentrations were examined under basal and stimulated (hypovolemic) conditions. Additionally, we examined changes in blood volume, kidney function, and plasma electrolyte and protein levels, as well as changes in plasma aldosterone concentrations. Intracerebroventricular administration of AM increased plasma AVP levels, whereas AM ribozyme treatment led to decreased plasma AVP levels under stimulated conditions. During hypovolemic challenges, AM ribozyme treatment led to an increased loss of plasma volume compared with control animals. Although overall plasma osmolality did not differ between treatment groups during hypovolemia, aldosterone levels were significantly higher and, consequently, plasma potassium concentrations were lower in AM ribozyme-treated rats than in controls. These data suggest that brain-derived AM is a physiological regulator of vasopressin secretion and, thereby, fluid homeostasis.     

Effect of spironolactone on the renin-aldosterone system in rats

PRA, PRC and the plasma concentration of aldosterone (Aldo) were measured in rats (Sp-rats) receiving a daily sc injection of Spironolactone, (Sp, 20 mg in olive oil) and in control rats (C-rats) receiving olive oil only. Animals were studied one day after starting treatment, 5 days on treatment or after 5 weeks on the study. PRA, PRC and Aldo were significantly increased in Sp-rats as compared to C-rats throughout all the study. In additional Sp-rats and C-rats, the urine volume, serum Na+ and K+ concentration, Na+ and K+ intake and the urinary excretion of Na+, K+ and aldosterone-18-glucuronide (UAldV) were serially measured during 5 weeks. The total radioactivity plasma clearance after an i.v. bolus injection of 3H-aldosterone was subsequently measured in (5 Sp-rats and 5 C-rats). No significant differences in serum Na+ and K+ concentration and in Na+ and K+ balance were observed between Sp-rats and C-rats. UAldV was significantly higher in Sp-rats than in C-rats during all the study. After 5 weeks on treatment the total radioactivity plasma clearance was significantly higher in Sp-rats than in C-rats. These results indicate that Sp, at high dosage, stimulates renin release and aldosterone secretion by a mechanism unrelated to alterations in Na+ and K+ balance.     

Influence of endogenous opioids on atrial natriuretic factor release during exercise in man

To evaluate to what extent opioid secretion in exercise induces the release of atrial natriuretic factor (ANF), six healthy male volunteers who were trained subjects, were submitted to two maximal exercise tests with and without (control) opioid receptor blockade by Naltrexone. Blood samples were drawn before (rest) and after exercise (post-exercise) in order to measure human ANF (alpha h ANF), beta-endorphin, plasma aldosterone concentration (PAC) plasma renin activity (PRA) and adreno-cortico trophic hormone (ATCH) by radio-immunological methods. Expired gas was collected during exercise to measure oxygen consumption. On average, the same maximal oxygen consumption (VO2max) during exercise was reached by all subjects with and without treatment. Plasma ANF level at rest slightly decreased after administration of Naltrexone; the response to physical exercise was significantly reduced by Naltrexone. There was no statistical difference between plasma levels of beta-endorphin, PRA and ACTH at rest nor in the post-exercise situation under the influence of Naltrexone. The PAC increased significantly at rest after Naltrexone administration but there was no statistical difference between both values after exercise. These data demonstrate that: (1) ANF secretion during exercise is influenced by the level of beta-endorphin in the plasma; (2) the possible inhibitory role of ANF on aldosterone secretion during exercise is probably over-ruled by the increase in plasma ACTH and PRA.     

Role of atrial natriuretic peptide in mineralocorticoid escape phenomenon in patients with primary aldosteronism

The withdrawal effect of spironolactone treatment on natriuresis was studied in relation to atrial natriuretic peptide (ANP) in five patients with primary aldosteronism due to adenoma. The patients had been treated with spironolactone for 2-3 months before they were admitted. After admission, blood pressure, body weight, and urinary excretion of sodium were measured daily. Venous samples were obtained twice a week for measurements of plasma levels of ANP, plasma renin activity (PRA), and plasma concentrations of aldosterone (PAC), cortisol, and deoxycorticosterone. The study was performed for 7 days during the treatment with spironolactone and for 18 days after stopping the administration. Plasma volume was determined two times, during the control period and on the 13th day after stopping spironolactone. Urinary sodium excretion decreased initially and returned to the control levels successively. Body weight and plasma volume increased, and blood pressure rose steadily. PRA and the plasma concentrations of cortisol and deoxycorticosterone decreased significantly (P less than 0.05); however, high levels of PAC did not alter significantly. Plasma ANP levels increased significantly (P less than 0.05) from 26 +/- 4 pg/ml during the control period to 195 +/- 47 pg/ml on the 13th day after stopping spironolactone. The data of the urinary sodium excretion showed the escape from sodium-retaining effect of aldosterone, and this escape could be explained by the increase in plasma ANP. Furthermore, ANP might contribute to the decrease in cortisol and deoxycorticosterone in plasma because of the direct inhibitory action of ANP on steroidogenesis.     

Role of angiotensin in body fluid homeostasis of mice: fluid intake,plasma hormones,and brain Fos

CD1 mice injected peripherally with either ANG I or ANG II failed to drink substantial amounts of water or NaCl, yet showed strong Fos immunoreactivity (ir) in subfornical organ (SFO). Mice injected with furosemide showed modest stimulation of NaCl intake either 3 or 24 h later, were hypovolemic, and showed elevated plasma renin activity (PRA). The pattern of Fos-ir in the brain after furosemide was similar to that seen after peripheral injection of ANG II. Mice became hypovolemic after subcutaneous injection of polyethylene glycol (PEG), showed large increases in PRA, aldosterone, and water intake, but did not show sodium appetite. PEG-treated mice had strong activation of SFO as well as other brain regions previously shown to be related to ANG-associated drinking in rats. ANG II appears to have a modified role in the behavioral response to fluid loss in mice compared with rats.     

Effect of Acipimox on Plasma Lipids and Glucose/Insulin in Pregnant Rats

To determine how a reduction in maternal hypertriglyceridemia during late pregnancy may affect glucose/insulin relationships, pregnant and virgin rats were orally treated with acipimox, a potent antilipolytic agent. In 20-day pregnant rats receiving 80 mg of acipimox, plasma triglycerides (TG), free fatty acids (FFA), and glycerol decreased more than in virgin rats shortly after the drug (up to 7 hours), when compared with animals treated with distilled water, whereas plasma glucose level was unaffected by the treatment in either group of rats. When acipimox was given every 12 hours from day 17 to day 20 of pregnancy, plasma TG, FFA, and glycerol levels progressively increased, whereas they either decreased or did not change in virgin rats receiving the same treatment, with no effect in plasma glucose levels in either group. Fetal body weight was lower than in controls in 20-day pregnant rats that received acipimox for 3 days. On day 20 of pregnancy, 3 hours after receiving acipimox or distilled water, rats received a 2 g glucose/kg oral load and it was found that the change in plasma glucose was similar in both groups, whereas the increase in plasma insulin was greater in pregnant rats treated with acipimox. However, no difference was found in either variable after the oral glucose load in virgin rats receiving acipimox or distilled water. No differences in plasma glucose levels were found after intravenous (IV) administration of insulin in pregnant rats treated or not treated with acipimox. In conclusion, present results show that administration of acipimox during the last days of gestation inhibited lipolysis and decreased fetal weight. Over a short period of time, in pregnant rats, reductions of plasma FFA and TG after acipimox treatment improved the glucose-induced insulin release, but did not seem to have any effect in peripheral insulin resistance.     

Renal effects of the acute inhibition of angiotensin-converting enzyme. I. 1) Studies during normal sodium and potassium balance]

We have investigated the effective role of angiotensin II on the renal function and urinary excretion of some prostanoids in healthy women submitted to different conditions of potassium balance. To this aim we have evaluated the effects of an acute inhibition of angiotensin converting enzyme by enalapril (E). The renal function was explored by clearance (cl.) method during induced hypotonic polyuria (oral water load followed by 5% dextrose solution infusion). During 60 min cl. period the urinary PGE2, 6-keto-PGF1 alpha and TxB2 were determined by RIA method. Each subject received paired studies, in absence and presence of E (10 mg administered per os 1 hour before the water load). Basal values of plasma renin activity (PRA) and urinary aldosterone (excreted during the 24 hours before the water load) were also determined by RIA method. This study protocol was applied in normal potassium balance (n = 6) and induced moderate potassium depletion (n = 6). This paper concerns the group in normal potassium balance in both absence (N3) and presence of E (N3.E). All subjects were submitted to normal dietary intake of sodium (150 mmol/d) and potassium (50 mmol/d). The basal values of PRA, urinary aldosterone and plasma electrolytes were in the normal range. The only significant effect produced by E was a reduction in mean arterial pressure, without significant changes in creatinine cl., urinary hydro-electrolyte excretions as well as urinary excretions of prostanoids.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma aldosterone, renin activity, and cortisol responses to heat exposure in sodium depleted and repeleted subjects.

The effect of 90-min heat exposure (46 degrees C, 35 mbar) on plasma aldosterone (PA) patterns was studied and the respective roles of plasma renin activity (PRA), adrenocorticotropin (ACTH), Na+ and K+ concentrations in the control of PA response were in investigated in eight subjects on a low sodium diet and in five subjects on a high sodium diet. In all subjects, transitory PA increases of varying importance were observed, which were not related to sweat losses (less than 1% bodyweight) or to rectal temperature rise. In sodium-repleted subjects, basal PA and PRA levels as well as heat-induced rises were low (mean PA peak level = 12.62 +/- 1.15 ng/100 ml). They were enhanced by sodium depletion and PA reached a mean peak level of 34.07 +/- 2.73 ng/100 ml. But, in both conditions, the heat-induced PA peaks were 3-times higher than the initial levels. PA correlated with PRA in all but one of the sodium-repleted subjects and in 6 of the 8 sodium-depleted subjects. ACTH release, as measured by plasma cortisol (PC) levels, occurred in those subjects who noted an increased feeling of annoyance and discomfort. Thus, PA correlated positively with PC in 4 sodium-depleted subjects. A high sodium intake improved heat-tolerance. Plasma K+ and Na+ concentrations were not significantly modified by exposure to heat. PA increases can occur without concomitant changes in PRA, PC, K+ or Na+, which suggests that an additional factor may play a role in aldosterone regulation during acute heat exposure.     

Glucocorticoid suppression enhances the 18-hydroxycorticosterone and aldosterone response to metoclopramide in man

18-Hydroxycorticosterone (18-OHB) is a precursor of aldosterone and is the only corticosteroid, other than aldosterone, that is synthesized predominantly in the zona glomerulosa. Administration of the dopamine antagonist, metoclopramide results in parallel rises in plasma 18-OHB and aldosterone levels without affecting the plasma levels of other aldosterone precursors. However, 18-OHB is a product of the zona fasciculata as well as the glomerulosa. Thus, it is possible that metoclopramide may stimulate zona fasciculata secretion of 18-OHB. In order to more selectively examine dopaminergic regulation of zona glomerulosa secretion of 18-OHB we have examined the effect of glucocorticoid suppression of the fasciculata on the 18-OHB and aldosterone responses to metoclopramide, 10 mg iv in 6 normal volunteers. Dexamethasone, 2 mg every 6 hours for 5 days, suppressed basal levels of cortisol, corticosterone, 18-OHB and aldosterone. Dexamethasone treatment had no effect on basal levels of PRA or PRA responses to metoclopramide. The 18-OHB and aldosterone responses to metoclopramide were enhanced (p less than .05) by dexamethasone suppression. The results suggest that dopaminergic mechanisms selectively suppress glomerulosa production of 18-OHB. Endogenous ACTH may inhibit zona glomerulosa production of 18-OHB and aldosterone in response to the dopamine antagonist, metoclopramide.     

Plasma renin activity and aldosterone response to furosemide after chronic growth hormone administration to deficient subjects

The plasma renin activity (PRA) and aldosterone responses to furosemide-induced diuresis were measured in seven children with growth hormone deficiency prior to, during and after the admistration of clinical grade human growth hormone (hGH). The furosemide-stimulated increases in PRA were unchanged from baseline values after one and eight months of hGH administration, but the plasma aldosterone concentrations were significantly increased over control values after eight months of hGH administration.Plasma cortisol concentrations as determined by competitive protein binding assay were measured with the 30-minute cosyntropin (Cortrosyn) test. A normal response as defined by a final level of at least 20 ug/100 ml was found in all children. Resting cortisol concentrations were unchanged during treatment with hGH but the mean increment and final levels were significantly diminished after 8 months of hGH administration. These data have not elucidated the mechanism by which clinical grade hGH improves diuretic-induced aldosterone responsiveness but diminishes cosyntropin stimulation of the adrenal in childhood.     

Involvement of sodium retention hormones during rehydration in humans

We investigated the relation between involuntary dehydration and the mechanisms affecting Na+ retention in the body, focusing on the renin-angiotensin-aldosterone system. Six adult males were dehydrated to 2.3% of their body weight by an exercise-heat regimen, followed by rehydration (180 min) with tap water (H2O-R) or 0.45% NaCl solution (Na-R). We measured plasma renin activity (PRA) and aldosterone levels (PA) before dehydration (control), after dehydration, and at 60, 120, and 180 min of rehydration. During the 3-h rehydration period, subjects, restored 51% of the water lost during H2O-R and 71% during Na-R (P less than 0.05). Plasma volume was reduced by an average of 4.5% after dehydration. After 180 min of rehydration, plasma volume restoration during Na-R was to 174% of that lost, and during H2O-R it was to 78% of that lost. We found significant correlations between the change in plasma volume and PRA (r = -0.70, P less than 0.001) and between PRA and PA (r = 0.71, P less than 0.001). In both recovery conditions, PRA increased significantly after dehydration (P less than 0.05) and decreased almost to the control level by 180 min of rehydration, at which time the plasma volume deficit was restored. The change in PA paralleled that in PRA. The rate of sodium excretion was correlated with PA levels in both groups (r = -0.58, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Renal Na+-K+-ATPase in weanling and adult spontaneously hypertensive rats

The interrelationships among plasma renin activity (PRA, ng AI/ml plasma/hr), aldosterone concentration (ng%), and renal Na+-K+-ATPase activity (mumole PO4/mg protein/hr) were studied in 9 weanling normotensive spontaneously hypertensive rats (SHR), 9 adult hypertensive SHR, and 9 weanling and 9 adult normotensive Wistar-Kyoto rats (WKY). All groups were placed on a normal (0.4% sodium) diet. PRA and plasma aldosterone, measured in samples drawn from the ether-anesthetized rat, were higher in weanling SHR (15.2 +/- 2.0, 37 +/- 4.2) than in WKY. PRA measured in samples collected from a separate group of unanesthetized weanling SHR was also greater than in age-matched WKY. In adult SHR, PRA (6.1 +/- 0.9) and plasma aldosterone (20.0 +/- 2.7) were decreased. During the weanling period Na+-K+-ATPase activity in SHR was not only greater than in age-matched WKY but was also increased compared to adult normotensive and hypertensive rats (137 +/- 9 weanling SHR, 89 +/- 7 weanling WKY, 73 +/- 11 adult SHR, 84 +/- 17 adult WKY). Thus, during the weanling period the renin-angiotensin-aldosterone (R-A-A) system and renal Na+-K+-ATPase activity are activated in SHR. The elevation of Na+-K+-ATPase activity may be due to increased aldosterone levels. It was noted, however, that plasma aldosterone was similar in adult WKY and weanling SHR, while Na+-K+-ATPase activity was higher in SHR. These findings involving R-A-A and renal Na+-K+-ATPase activity prior to the elevation of blood pressure suggest that the kidneys may play a role in the initiation of hypertension in SHR.     

Effect of prostaglandin E1 on renin and aldosterone in hypertensive patients.

The effect of prostaglandin E1 (PGE1) on plasma renin activity (PRA) and plasma aldosterone concentration (PAC) was studied in the hypertensive subjects treated with or without 75 mg indomethacin or 60 mg propranolol for a week. Subsequent to the treatment with indomethacin for a week, PRA and PAC levels were decreased as compared to the control, without changes in the blood pressure and heart rate. During the infusion of PGE1, the blood pressure was decreased and the pulse rate was increased. PRA and PAC levels were also elevated. These changes of parameters were not different between the control and the indomethacin-treated subjects. PRA and PAC were suppressed after the treatment with propranolol. With the infusion of PGE1, the level of PRA was not significantly elevated, while, PAC was significantly increased by the infusion of 100 ng/Kg/min of PGE1. During the infusion of PGE1, the blood pressure was decreased while the pulse rate was increased in the subjects treated with propranolol. However, the elevation of the pulse rate was less remarkable than the control. These data indicate that PGE1 have important roles in the regulation of the release of renin and aldosterone. These findings also suggest that PGE1 may act to stimulate the secretion of aldosterone in man.     

Changes in the renin-angiotensin-aldosterone system in rats of both sexes submitted to chronic hypobaric hypoxia

The effect of moderate chronic hypobaric hypoxia (CHH) on the renin-angiotensin-aldosterone system has been analysed in male and female intact and castrated rats. The experimental animals were submitted to a simulated altitude of 4,400 m during ten weeks. Half of the experimental and half of the control animals were castrated at three weeks of age. Arterial pressure (AP) was measured once a week during the whole experimental period. Blood samples were obtained by decapitation at the end of the study. Red cell volume, plasma renin activity (PRA), plasma angiotensinogen (Ao) and aldosterone concentration (ALDO) were determined in the blood samples. Results have shown that the female animals subjected to CHH had lower levels of AP than the control female rats during all the studied periods whereas the AP of male hypoxic rats was only transiently diminished. All these changes were abolished by castration. PRA was not altered in either sex. The enzymatic complex was higher in male than in female control animals and decreased after castration in both hypoxic and control male rats. Ao was decreased by CHH in both sexes of intact rats and in female castrated animals. The renin substrate was higher in male than in female intact rats and decreased after castration in male animals. ALDO was increased after CHH only in male rats. Control female rats have higher levels of ALDO than male animals. Changes in the renin-angiotensin-aldosterone system related to CHH and also significant differences between sexes suggest that adrenal and gonadal corticosteroids may be involved in the main alterations presently observed.