CONTROL OF PLASMA ALDOSTERONE IN SUPINE ANEPHRIC MAN

Plasma aldosterone, plasma cortisol, plasma renin activity and the serum concentrations of sodium and potassium were determined at short time-intervals in four supine anephric patients. Two patients were studied the night before and the night following haemodialysis. In both patients increases in plasma aldosterone occurred without concomitant alterations in serum sodium and serum potassium while plasma renin activity was uniformly undetectable. However, the observed fluctuations in plasma aldosterone were markedly more pronounced the night following haemodialysis. Under the latter conditions, typical secretory episodes of aldosterone occurred. The onset of these secretory episodes was not associated with simultaneous increases in plasma cortisol, whereas before haemodialysis changes in plasma aldosterone were paralleled by those in plasma cortisol. Except for the peak values of the secretory episodes of aldosterone, plasma aldosterone was markedly higher the night before than the night following haemodialysis. These differences between pre- and post-haemodialysis aldosterone values correlated well with serum potassium, which was approximately 1 mEq/1 lower the night following haemodialysis. Two patients were studied the night following haemodialysis under normal conditions and with suppression of ACTH secretion by dexamethasone. Under both conditions, a typical episodic secretion of aldosterone was observed. In both patients plasma ACTH was below the lower limit of detectability (<20 pg/ml) under dexamethasone medication. It was concluded from our experiments that: (1) the differences between pre- and post-haemodialysis aldosterone values reflect a direct influence of potassium on the secretion of aldosterone; (2) the fluctuations in plasma aldosterone which were observed the night before haemodialysis were mostly probably mediated through ACTH; and (3) an unknown factor had caused episodic secretion of aldosterone the night following haemodialysis.     

The 24-h cortisol secretory pattern in Cushing's syndrome

The 24-h plasma cortisol profile was obtained at 20-min intervals in 18 patients with Cushing's syndrome (10 with Cushing's disease, 5 with adrenal adenoma, 2 with ectopic ACTH secretion and 1 of questionable aetiology). The mean cortisol level was maximum in the case of ectopic ACTH secretion. The coefficient of variation of cortisol levels was subnormal in all except 2 subjects. Periodogram calculations, providing a best-fit curve (B F C) for each profile, showed that the existence of a significant baseline variation is a frequent feature. In certain cases, it is compatible with the persistence of a true circadian rhythm (2 patients with Cushing's disease; 1 patient with adrenal adenoma). The alteration of plasma cortisol pulsatility is much more pronounced in patients with adrenal adenoma than in patients with Cushing's disease. This is consistent with the hypothesis of a predominantly tonic secretion blunting the episodic hormone release. In 9 patients with Cushing's disease, the plasma cortisol pattern was suggestive of a combination of episodic cortisol release under CRF control and of continuous cortisol secretion due to constant stimulation from an autonomous ACTH source. Two cases were possibly of hypothalamic origin, as suggested by the presence of enhanced cortisol pulsatility and of a normal circadian amplitude. The analysis of the 24-h profile of plasma cortisol in Cushing's syndrome contributes to our understanding of the physiopathological mechanisms underlying this disorder and may help the diagnosis of its aetiology.     

Adrenocorticotropin-stimulated secretion of aldosterone and cortisol, computed from plasma and red blood cell measurements.

The dynamic response of the adrenal cortex to ACTH infusion is analyzed by simulating the distribution, binding, and metabolism of cortisol and aldosterone in a multicompartmental model. The model includes the effects of temperature and cortisol concentration on aldosterone binding in plasma and the distribution between plasma and red blood cells, as verified by new observations. The secretion rates of cortisol and aldosterone were computed from serial measurements of plasma concentrations of endogenous steroids and infused tracers. The model was validated by observations after iv injection of a bolus of cortisol. Nineteen normal volunteers were studied on the fourth day on a diet containing 10 meq sodium. Endogenous ACTH was suppressed by dexamethasone, and alpha-1-24ACTH was infused at two different rates in various sequences over a 4-h period. During each hour of constant ACTH infusion, plasma cortisol continued to increase, while plasma aldosterone rose quickly, reaching a plateau within 20--30 min. Cortisol secretion approached a maximim rate after 20--30 min of ACTH infusion; the continued increase of plasma cortisol resulted from the slow equilibrium with other compartments. Aldosterone secretion rose quickly to a peak and then declined to a lower level after 20 min of ACTH infusion; the lower rate of secretion was maintained for the duration of the constant infusion of ACTH, falling abruptly within a few minutes after stopping the infusion. The characteristic differences in plasma steroid responses to various sequences of ACTH infusions can be explained by the more rapid changes in aldosterone secretion and the different clearance rates of cortisol and aldosterone, which vary with plasma cortisol concentration. The temperature at which blood is separated significantly affects plasma aldosterone measurements.     

Rhythm characteristics of plasma renin, aldosterone and cortisol in five subtypes of mesor-hypertension

The possible role of the renin-angiotensin system and ACTH in controlling the temporal organization of circadian rhythm of aldosterone was studied in patients with mesor-hypertension (MH) by simultaneous radioimmunological determinations of within-day changes in plasma renin, aldosterone and cortisol. Thirty-nine uncomplicated, untreated mesor-hypertensive patients, divided in subtypes, were examined. The interrelationship between the rhythm components revealed that the circadian cyclicity of aldosterone in both mesor-normotensive and mesor-hypertensive subjects, with either normal or high renin patterns, has a similar timing in acrophase with renin periodicity, which leads the circadian cortisol rhythm. In low-renin mesorhypertensive subjects a circadian rhythm of aldosterone and cortisol, but not of renin, remains demonstrable. The confidence limits of the estimated acrophase for circadian cortisol rhythm do not, however, overlap the confidence arcs of the aldosterone phase. These findings suggest that in normal or high renin MH subjects the aldosterone rhythmicity is mainly controlled by the renin-angiotensin system. Conversely in low-renin MH subjects the temporal organization of the aldosterone circadian sequences seems to be completely independent of renin-angiotensin control.     

Response of plasma ACTH and adrenocortical hormones to potassium loading in essential hypertension

The effect of potassium loading on plasma adrenocortical hormones concentrations in 9 patients with essential hypertension (EH) was investigated. The plasma renin activity (PRA), plasma concentrations of growth hormone (GH), ACTH, cortisol, deoxycorticosterone (DOC), 18-hydroxy-deoxycorticosterone (18-OH-DOC) and aldosterone, and serum electrolytes were measured before and after potassium chloride (KC1) infusion (0.33 mEq/kg/h, for one hour). The KC1 infusion caused significant increases in serum potassium levels and plasma levels of GH, ACTH, cortisol, DOC, 18-OH-DOC and aldosterone, while PRA remained unchanged. Regression analysis at 30 min revealed significant positive correlations between delta ACTH and delta cortisol, between delta ACTH and delta DOC, between delta ACTH and delta 18-OH-DOC. However, the relationship between delta ACTH and delta aldosterone was not statistically significant. These results suggest that (1) acute potassium loading causes a significant increase in the plasma ACTH level and increased levels of adrenocortical hormones may be produced by increased ACTH secretion, and (2) it may be considered that a part of the increased level of plasma aldosterone following acute potassium loading may arise from increased ACTH secretion in EH.     

Circadian pattern of circulating plasma ACTH, cortisol, and aldosterone in patients with beta-thalassemia

Plasma levels of ACTH, cortisol, and aldosterone were measured for an entire day every 2 h, starting from midnight, in 4 healthy subjects, and in 4 patients with beta-thalassemia, without evidence for any endocrine disease. The subjects, after synchronized standard life conditions for 10 days, were held in constant supine position during the study. The data were analysed by the "cosinor" method. The results show significant circadian rhythms for the three biological variables in healthy subjects. In the thalassemic patients a significant circadian rhythm was detected only for cortisol and aldosterone. No rhythm was demonstrated for ACTH in the patient group. While no differences were found in mesors and acrophases for the three hormones between the two groups, a significant difference was observed regarding amplitudes. These data suggest that in beta-thalassemia, the secretion rhythmicity of ACTH is modified, whereas the adrenal cortex maintains its own physiologic rhythmicity in hormone secretion.     

Japanese family with glucocorticoid-remediable aldosteronism diagnosed by long-polymerase chain reaction.

We report a Japanese family with glucocorticoid-remediable aldosteronism (GRA) in whom gene abnormality was identified by the long-polymerase chain reaction (PCR) method. The proband was a 21-year-old female incidentally found to have high blood pressure (173/107 mmHg). Laboratory tests showed hypokalemia (3.7 mmol/l), and high plasma aldosterone concentration (PAC, 234 pg/ml) with suppressed plasma renin activity (PRA, <0.1 ng/ml/h). The circadian rhythm pattern and the results of a rapid adrenocorticotrophic hormone (ACTH) test indicated ACTH-dependent changes in PAC. Imaging studies showed no adrenal mass on either side. A dexamethasone (Dexa) suppression test (1.0 mg/day orally for 7 days) showed a marked decrease of PAC 2 days after administration, and this decreased level was maintained throughout Dexa administration. High blood pressure and hypokalemia also improved during Dexa treatment. The proband's younger sister was 19 years old and had hypertension, PAC of 231 pg/ml, and PRA <0.1 ng/ml/h. The mother was 53 years old and had hypertension, PAC of 98.5 pg/ml, and PRA <0.1 ng/ml/h. The proband's elder sister was a 22-year-old normotensive with PAC of 110 pg/ml and PRA of 0.1 ng/ml. Long-PCR was performed for detection of the chimeric gene associated with GRA, using DNA samples from all four cases and two normal control subjects. Although the aldosterone synthase gene was expressed among all DNA samples, the chimeric gene was detected only in the proband, her younger sister and her mother. Our clinical data and genetic investigation confirmed the presence of GRA in this Japanese family.     

The Effect of Captopril on Renin,Angiotensin II,Cortisol and Aldosterone During Acth-Infusion in man

Prolonged low-dose ACTH infusion (5 or 10 iU/24h) leads to a transient increase in plasma renin activity and angiotensin II concentration in normal man. In order to find out whether the increase in angiotensin II stimulates aldosterone secretion, 12 normal men received ACTH (10 IU/24h) for 34 hours altogether, 6 with and 6 without simultaneous administration of captopril, 50 mg every 6 hours.

Captopril prevanted the increase in plasma angiotensin II during ACTH infusion and lowered its levels below those on the control day two hours after a new dose of the converting enzyme inhibitor was given. The increase in plasma cortisol was similar in both groups. The increase in plasma aldosterone was significantly blunted by captopril. The early blood pressure rise and the kaliuresis during ACTH infusion were also significantly decreased in the captopril group. These results suggest that angiotensin II mediates in part the effect of ACTH on aldosterone and blood pressure during the first 2 days of infusion. Since captopril reduced plasma angiotensin II for some time below normal, it is alternatively possible that ACTH requires normal plasma angiotensin II levels for a full effect on aldosterone secretion.     

RESPONSE OF PITUITARY-ADRENAL AXIS TO CORTICOTROPHIN RELEASING HORMONE IN PATIENTS WITH CUSHING'S DISEASE BEFORE AND AFTER KETOCONAZOLE TREATMENT

Ketoconazole is an antimycotic agent and a potent inhibitor of gonadal and adrenal steroidogenesis. It has been used successfully as a palliative treatment of Cushing's syndrome due to its ability to lower Cortisol production. However, the effects of ketoconazole on ACTH and aldosterone secretion have not yet been clarified. We evaluated the effect of ovine corticotrophin releasing hormone (oCRH) (100 μg bolus) on plasma ACTH, Cortisol and aldosterone levels in six patients with Cushing's disease before and after 4 to 6 weeks of treatment with ketoconazole 600 mg/d. Before treatment, plasma Cortisol levels were high and significantly increased after oCRH stimulation in all cases, while various patterns of aldosterone secretion were observed. Patients with higher levels showed a greater response to oCRH, while two patients with very low aldosterone showed no response. ACTH showed a marked rise after oCRH administration in all patients with a maximum peak at 30-45 min. After ketoconazole treatment, both plasma Cortisol and aldosterone were lowered and their response to oCRH was impaired. Basal ACTH levels were increased in four patients and ACTH response to oCRH was enhanced in all, compared to pretreatment. These findings confirm the inhibitory action of ketoconazole on basal and stimulated Cortisol secretion. A similar inhibition affected aldosterone production, indicating that ketoconazole also interferes with the mineralocorti-coid pathway. The enhanced response of ACTH to oCRH after the administration of ketoconazole argues against an inhibitory effect of this agent at the pituitary level and might best be explained by reduced negative Cortisol feedback.     

Circadian rhythmicity of ACTH and corticosterone in the rat

The circadian secretion of ACTH and corticosterone was assessed by measuring immunoreactive ACTH concentration in the plasma and ACTH content in the anterior and posterior pituitary over a 30 h period in groups of both male and female rats and comparing these data to fluorometric corticosterone concentration in the plasma and corticosterone content in the adrenal. A circadian rhythm of plasma corticosterone levels and adrenal content was apparent in both males and females with the highest levels at the onset of darkness. In contrast, there was no significant circadian rhythm in plasma ACTH levels or anterior or posterior ACTH pituitary content. Because the ACTH and corticosterone rhythms were dissociated, rhythmic corticosterone secretion is not entirely dependent on ACTH secretion.     

The effects of fadrozole hydrochloride on aldosterone secretion in healthy male subjects.

The aim of this double blind placebo-controlled cross-over study was to evaluate the effects of fadrozole, a new oral nonsteroidal aromatase inhibitor, on basal and stimulated cortisol and aldosterone secretion at a daily dosage of 4 mg given for 14 days to eight healthy men. After 2 weeks of treatment, fadrozole, compared with placebo, effectively suppressed plasma estrogen levels (P less than 0.05 at 0800 h), but did not affect glucocorticoid secretion either under basal conditions or after stimulation with ACTH. Basal plasma aldosterone levels were not significantly different with fadrozole treatment compared to those after placebo treatment. However, compared with pretreatment values, basal aldosterone secretion appeared impaired (P less than 0.05). A statistically significant blunting of the responses of plasma aldosterone to ACTH (P less than 0.01) and upright posture (P less than 0.01) after fadrozole compared with placebo treatment further indicated that fadrozole impaired basal aldosterone secretion. This attenuation of aldosterone secretion was accompanied by a rise of PRA in the basal condition (P = 0.05) and after stimulation by 40 mg furosemide (P less than 0.01) and upright posture (P less than 0.01). An increase in deoxycorticosterone was observed after fadrozole treatment compared with pretreatment values (P less than 0.01) and after stimulation with ACTH compared with placebo (P less than 0.05). This study confirms that fadrozole given in daily doses of 4 mg is an effective aromatase inhibitor which does not affect glucocorticoid secretion. However, this dose may induce an impairment of aldosterone secretion which is modest and revealed mainly under specific stimulatory conditions, and does not lead to clinical symptoms of hemodynamic dysregulation or a relevant disturbance of serum electrolytes.     

The effect of dexamethasone on the 24-hour profiles of adrenocorticotropin and cortisol in Cushing's syndrome

ACTH and cortisol are normally secreted episodically rather than continuously. This characteristic of episodic secretion is preserved in patients with Cushing's syndrome. To determine whether exogenous glucocorticoids modulate this pulsatility and to study its possible etiological implications, we obtained 24-h plasma cortisol profiles in seven patients with Cushing's syndrome (five Cushing's disease, one adrenal adenoma, and one bilateral adrenal cortical macronodular hyperplasia) before and during suppression with various doses of dexamethasone [low (0.5 mg, every 6 h), high (2 mg, every 6 h), and very high (4 mg, every 6 h)]. Simultaneous 24-h plasma ACTH profiles were obtained in two patients with Cushing's disease. Blood was drawn at 30-min intervals for 25 h. Individual profiles were analyzed to determine the 24-h mean level, the presence of a circadian component and its amplitude, and the number and magnitude of significant secretory pulses over the 24-h span. The concordance between significant ACTH and cortisol pulses also was quantified. Baseline values in patients were compared to those in seven normal subjects. Under basal conditions, the 24-h mean cortisol level was 3- to 4-fold higher than normal in all patients with Cushing's syndrome. In contrast, the basal 24-h mean ACTH level was normal in one, and slightly elevated in the other of the two patients with Cushing's disease in whom plasma ACTH concentrations were measured. However, in contrast to the normal subjects, all ACTH values were above 10 pg/ml even during the period of minimal secretion. Basal circadian variation in adrenocortical activity, albeit of reduced amplitude, was found in four of five patients with Cushing's disease; it was absent in the patient with adrenal adenoma. Low dose dexamethasone reduced the 24-h mean cortisol level and increased the amplitude of the circadian rhythm, unmasking a diurnal rhythm in the single patient with Cushing's disease in whom no significant circadian periodicity was present in the basal condition. This effect was further increased with the high dose of dexamethasone, which concomitantly reduced the number and increments of the secretory pulses. A lesser effect was found in the patient with bilateral nodular hyperplasia, and no effect was seen in the patient with adrenal adenoma. ACTH pulsatility, but not diurnal rhythm, also was dampened by dexamethasone. Reduction in the magnitude, but not the number, of ACTH secretory pulses by dexamethasone produced a reduced concordance ratio of ACTH with cortisol pulses of 0.39, compared to 0.64 in the basal state.(ABSTRACT TRUNCATED AT 400 WORDS)     

Diurnal variation and responses of corticoids to dexamethasone and ACTH before and after adrenal surgery in primary aldosteronism

We studied diurnal variation and the responses of plasma corticoids to dexamethasone and ACTH before and after adrenal surgery in 11 patients with primary aldosteronism. Diurnal variation of plasma corticoids was examined in all cases. Before adrenal surgery, plasma aldosterone (Ald) was higher at all times, deoxycorticosterone (DOC) was high value at 5:00 and then normal value, 11-deoxycortisol (S) was high value at 5:00 and 9:00, thereafter normal value, while corticosterone (B) and cortisol (F) were almost normal value at all times. The circadian rhythm was observed in these corticoids. Dexamethasone (2 mg/day) was administered to 8 patients for 10 days. Plasma Ald and DOC were significantly suppressed only at 5:00, while B, S and F almost suppressed at all times. After dexa suppression, the circadian rhythm of Ald still observed, while the diurnal variation of the other corticoids was even. ACTH (1 microgram) was injected intravenously to 9 patients. Responses of DOC, B and Ald were higher, and of S and F were almost normal. Diurnal variation of plasma corticoids was observed after 1 month of adrenal surgery. Ald was lower, the other corticoids were normal values. ACTH (1 microgram) was injected to the same case before surgery. Responses of these corticoids to ACTH were slightly lower. Contents of Ald in adenoma tissues were higher than those in adjacent and normal adrenal tissues, and the contents of the other corticoids in adenoma tissue were almost normal value. As these results showed, before surgery these corticoids were secreted from adenoma without ACTH, although these were responsible to ACTH, and the presence of regulative factor of circadian rhythm except ACTH was suggested. After surgery, not only the responses to ACTH of mineralocorticoids but these of glucocorticoids decreased.     

Differing effects of metoclopramide and adrenocorticotropin on plasma aldosterone levels in glucocorticoid-suppressible hyperaldosteronism and other forms of hyperaldosteronism

To investigate possible dopaminergic effects on aldosterone production, we administered the dopamine antagonist metoclopramide to 11 normal subjects, 8 patients with primary aldosteronism due to adenoma or hyperplasia, and 5 other patients with the glucocorticoid-suppressible form of hyperaldosteronism (GSH). All subjects except for those with GSH responded to metoclopramide with an increase in plasma aldosterone concentration even when endogenous ACTH was suppressed by dexamethasone pretreatment. This increase occurred without apparent mediation of other recognized stimuli for aldosterone secretion. In contrast, the patients with GSH failed to show any aldosterone response while receiving dexamethasone, but demonstrated a rise in plasma aldosterone concentration when dexamethasone was withheld. The responses in the patients with both forms of primary aldosteronism were greater in magnitude than in the normal subjects or in the subjects with GSH when not receiving dexamethasone. These studies, while demonstrating differences between the subtypes of hyperaldosteronism in their responsiveness to metoclopramide, indicate that ACTH or some other factor may exert a permissive effect in GSH for the aldosterone response to metoclopramide. A graded infusion of ACTH revealed a greater aldosterone response in GSH compared to that in the other groups, further suggesting the importance of ACTH in this disorder.     

On the role of dopamine receptors in aldosterone secretion

We studied the effects of infusion of dopamine (4 microgram/kg/min for 120 min) alone or with domperidone infusion (235 microgram/min for 120 min) on aldosterone secretion before and after stimulation by ACTH (0,5 mg i.v.) in normal subjects. We also studied the effects, of pimozide (12 mg p.o.), of domperidone infusion (235 microgram/min for 120 min) before and after stimulation with ACTH (0,5 mg i.v.) on aldosterone secretion in two other sets of normal subjects. The infusion of dopamine does not modify the basal secretion of aldosterone whereas in other trials it caused reduction (P less than 0,05) of blood aldosterone response to ACTH versus controls. Domperidone and pimozide, D2 antagonist, do not modify the aldosterone secretion before and after ACTH stimulation. Furthermore domperidone does not remove inhibition of dopamine on aldosterone response to ACTH. We can exclude an action of central or peripheral D2 dopaminergic receptors in aldosterone secretion in man. Dopamine, which does not cross the blood brain barrier, reduced the blood aldosterone response to ACTH; for those reasons we can hypothesize that receptors D1, stimulated by dopamine modulate aldosterone secretion.     

Plasma cortisol concentrations in Atlantic salmon, Salmo salar: episodic variations, diurnal change, and short term response to adrenocorticotrophic hormone

Short term episodic peaks 1-2 hr in duration in plasma cortisol levels were observed in adult Atlantic salmon. These results support the concept that episodic secretion of corticosteroids may be a characteristic feature of the vertebrate adrenal/interrenal regulatory system and provide an explanation for the variability frequently observed in plasma cortisol concentrations in salmonids. Plasma cortisol levels also varied throughout the light-dark cycle and mean concentrations were higher during the night. High frequency variations in plasma cortisol levels (with a time scale of minutes rather than hours) were not observed. Porcine adrenocorticotrophic hormone (ACTH) and ACTH1-24 but not alpha-melanocyte-stimulating hormone (alpha-MSH) increased plasma cortisol levels 10 min after injection. The change in plasma cortisol levels after injection of 1 mU/kg porcine ACTH was of similar magnitude and duration as endogenous episodic variations. Plasma cortisol levels during episodic peaks, circadian changes, or after ACTH injection were less than the binding capacity of the "high" affinity protein binding system for cortisol. Hence, the unbound cortisol concentration is a linear function of the total cortisol concentration. Whereas episodic release of cortisol is indicated here, the physiological importance of this mode of hormone secretion is unclear. Plasma glucose levels were unaffected up to 2 hr after injection of ACTH and did not show close temporal correlation with endogenous episodic peaks in plasma cortisol.     

Dopaminergic Modulation of Corticosteroid Responses to Angiotensin II in Man

This study was designed to investigate dopaminergic mechanisms involved in the control of corticosteroid secretion in man. Plasma cortisol, corticosterone, 11-deoxycorticosterone, 18-hydroxycorticosterone (18-OHB), and aldosterone responses to graded doses of angiotensin II and ACTH were evaluated in six healthy male volunteers with and without treatment with the dopamine agonist bromocriptine (BEC). Angiotensin II infusion resulted in parallel responses of 18-OHB and aldosterone without affecting other precursors of the aldosterone biosynthetic pathway. BEC (2.5 mg tid for 6 days) markedly suppressed basal supine plasma 18-OHB levels without affecting basal levels of aldosterone. Basal supine plasma corticosterone levels were increased after BEC treatment. BEC treatment inhibited the 18-OHB and aldosterone responses to graded infusions of angiotensin II. Plasma 18-OHB responses to ACTH infusion were not altered by BEC treatment. Other factors known to affect aldosterone and 18-OHB secretion such as plasma renin activity and serum electrolytes were not altered by BEC administration. These results suggest that angiotensin-mediated 18-OHB and aldosterone secretion is selectively inhibited by dopaminergic mechanisms.     

Calcitonin gene-related peptide modulates adrenal hormones in conscious dogs.

The effects of a small dose (2 pmol/kg) of human calcitonin gene-related peptide I on plasma renin activity and hormones, including, aldosterone, ACTH, cortisol, AVP and ANH, were investigated in 14 conscious dogs. In addition, we studied the effects of calcitonin gene-related peptide on aldosterone secretion when it is stimulated by angiotensin II and ACTH. An intravenous bolus injection of 2 pmol/kg of calcitonin gene-related peptide raised plasma renin activity (by 216%, p less than 0.05), ACTH (by 85%, p less than 0.05), AVP (by 89%, p less than 0.05), and ANH (by 36%, p less than 0.05). Despite the elevation of plasma renin activity, aldosterone was decreased (by 52%, p less than 0.05). Cortisol did not change significantly. Infusion of 1 pmol.kg-1.min-1 of angiotensin II produced an elevation of aldosterone (by 186%, p less than 0.01), which was completely inhibited by pretreatment with an injection of 2 pmol/kg of calcitonin gene-related peptide. On the other hand, aldosterone secretion stimulated by ACTH was not altered significantly by pretreatment with an injection of 2 pmol/kg of calcitonin gene-related peptide. These results suggest that calcitonin gene-related peptide inhibits aldosterone secretion, especially when aldosterone is stimulated by angiotensin II. In addition, calcitonin gene-related peptide may be involved as an endocrine modulator in the physiological control of other several hormones closely related to the hemodynamics.     

Aldosterone responses to angiotensin II, adrenocorticotropin, and potassium in chronic experimental diabetes mellitus in rats

To investigate alterations in aldosterone secretion in diabetes mellitus, the effects of angiotensin II, ACTH, and potassium on aldosterone secretion were examined in conscious unrestrained streptozotocin-induced diabetic rats (60 mg/kg, 12 weeks before study). In chronic experimental diabetic rats where PRA, plasma aldosterone concentration, and urinary excretion of prostaglandin E2 were significantly decreased, a significant attenuated response of aldosterone secretion was demonstrated after infusion of angiotensin II, ACTH, or potassium. Yet the plasma fluorogenic corticosteroids response to ACTH in diabetic rats was not significantly different from that in control rats. After acute potassium infusion (0.30 meq/kg X min), plasma potassium levels in diabetic rats were significantly higher than in control rats, although immunoreactive insulin levels remained unchanged compared to the significant elevation in control rats. These results suggest that defects in aldosterone synthesis exist in chronic experimental diabetic rats and that potassium homeostasis is impaired during acute potassium loading. This change in potassium homeostasis may be related to both insulin and aldosterone deficiencies.     

Primary Aldosteronism: Effects of Inhibition of ACTH and Potassium Administration on Plasma Aldosterone Concentration

The relative roles of ACTH, angiotensin and potassium in influencing aldosterone secretion in primary aldosteronism were assessed by direct or indirect means. In untreated patients with primary aldosteronism caused either by adrenal adenoma or hyperplasia plasma aldosterone and cortisol concentrations fluctuated in unison and dexamethasone reduced both hormones markedly. Only when renin-angiotens in system was greatly activated and plasma potassium normalized by medical treatment was dexamethasone less successful in lowering plasma aldosterone concentration. Potassium infusion of 10, 20 and 30 mEq/hr in patients with adenoma failed to elicit any increase in plasma aldosterone concentration despite significant increases in plasma potassium levels. These results suggest that patients with primary aldosteronism due to adrenal adenoma are relatively more sensitive to small changes in plasma ACTH level than those in plasma angiotensin or potassium levels. In recumbent patients with adrenal hyperplasia ACTH also modulates plasma aldosterone concentration.