Fall In Aldosterone Research Articles

Beneficial hemodynamic, endocrine, and renal effects of urocortin in experimental heart failure: Comparison with normal sheep

ObjectivesThe goal of this study was to determine the bioactivity of urocortin (Ucn) in experimental heart failure (HF). BackgroundUrocortin may participate in cardiovascular function and pressure/volume homeostasis. Its effects in HF are unknown. MethodsEight normal sheep and eight sheep with pacing-induced HF received ovine Ucn (10, 50, and 100 mg intravenous boluses at 2-h intervals) in vehicle-controlled studies. ResultsUrocortin boluses dose-dependently increased plasma Ucn (p < 0.001). Pharmacokinetics were similar in normal and HF sheep with half-lives approximating 1.3 and 19.5 h for the first and second phases, respectively. In HF, cardiac output increased (twofold), while peripheral resistance, left atrial pressure (both 50% falls: p < 0.001), and mean arterial pressure (p < 0.05) fell. In normal sheep, changes in peripheral resistance and atrial pressure were blunted and in arterial pressure were directionally opposite. Urocortin induced persistent, dose-dependent falls (30% to 50%) in plasma vasopressin, renin activity, aldosterone, natriuretic peptides (all p < 0.001), and endothelin-1 (p < 0.05) in HF sheep, while adrenocorticotrophic hormone and cortisol levels rose acutely (both p < 0.001). In comparison, Ucn in normal sheep resulted in a similar rise in cortisol and fall in aldosterone, no significant effects on plasma renin activity and natriuretic peptides, and a rise in vasopressin. Urocortin produced dose-dependent, sustained increases in urine volume (twofold, p < 0.01), sodium excretion (>9-fold rise, p < 0.001), and creatinine clearance (p < 0.001) in HF sheep. No significant renal effects were observed in normal sheep. ConclusionsUrocortin has profound and sustained hemodynamic, hormonal, and renal effects in experimental HF. Urocortin may have a role in pressure/volume homeostasis in HF and may provide a novel therapeutic approach to this disease.

Aldosterone does not regulate amiloride-sensitive Na(+) transport in the colon of the Australian common brushtail possum, Trichosurus vulpecula.

Plasma aldosterone concentrations and the magnitude of amiloride-sensitive Na(+) transport in the proximal and distal colon of newly caught wild possums, and of possums maintained on either low or high Na(+) diets, were determined to evaluate their role in the regulation of salt content of faeces in common brushtail possums. Wild animals had a plasma aldosterone concentration of 439+/-115 pmol l(-1) and high levels of amiloride-sensitive Na(+) transport in both the proximal and distal colon. Animals maintained on a low Na(+) diet for 14 days excreted very little Na(+) in the urine and had an elevated aldosterone concentration (840+/-246 pmol l(-1)), but levels of amiloride-sensitive Na(+) transport in the proximal and distal colon were similar to those in wild animals. Conversely, while provision of a high Na(+) diet (7 days or 14 days) resulted in increased urinary Na(+) excretion and a fall in aldosterone (approximately 250 pmol l(-1)), there was no reduction in the amount of amiloride-sensitive Na(+) transport in either the proximal or distal colon. These data strongly indicate that aldosterone does not regulate amiloride-sensitive Na(+) transport in the colon of possums and that the colon is not involved in the regulation of salt content of the faeces in this species.

Atrial natriuretic peptide administration to normal and salt depleted rats — Effects on digoxin-like immunoreactive factor, aldosterone, acth, and renal function

In view of the known interrelationships between renin, aldosterone, and atrial natriuretic peptide (ANP), we sought to examine whether there also exists an interaction between ANP and digoxin-like immunoreactive factor (DLIF). We therefore studied the effects of ANP administration on normal and salt-depleted rats, and measured the effects on blood pressure, urine output, glomerular filtration rate, sodium excretion, aldosterone, ACTH, and DLIF levels. ANP administration resulted in a significant elevation of sodium excretion and glomerular filtration rate and a fall in blood pressure. DLIF concentrations in plasma rose significantly, as did urinary DLIF excretion. ANP administration resulted in a fall in aldosterone as well as ACTH. These observations suggest that ANP has a direct inhibitory effect on ACTH secretion. Our findings support the concept of an interrelationship between ANP and DLIF.

Dexamethasone-suppressible hyperaldosteronism. Adrenal transition cell hyperplasia?

Dexamethasone-suppressible hyperaldosteronism is a rare familial syndrome in which hypokalemia, suppression of plasma renin concentration, and elevated aldosterone secretion are corrected by treatment with glucocorticoids. Regulation of adrenocortical function and body electrolytes was studied in two affected brothers. Both were hypertensive (210/128 and 160/106 mm Hg) with hypokalemia (3.3 and 3.5 mM) and low plasma renin concentrations. Aldosterone was elevated intermittently with levels as high as 45 ng/dl (normal range, 4-16 ng/dl). Cortisol concentrations were normal but were correlated with aldosterone levels (r = 0.9 and 0.7). Concentrations of 11-deoxycorticosterone (19 and 21 ng/dl; normal range, 4-16 ng/dl) and 18-hydroxycortisol (1000 and 950 ng/dl; normal range, 34-150 ng/dl) were elevated, and diurnal changes in both were the same as those seen with aldosterone. Infusion of adrenocorticotropic hormone (ACTH) caused exaggerated increases of aldosterone, 11-deoxycorticosterone, and 18-hydroxycortisol; cortisol response was normal. A 4-week trial of dexamethasone normalized blood pressure and caused a natriuresis, a fall in aldosterone, and a rise in plasma renin. Administration of ACTH after dexamethasone treatment again caused exaggerated increases of aldosterone. Aldosterone did not respond to angiotensin II before dexamethasone therapy (r = 0.01), but it showed a normal response after therapy (r = 0.8, p less than 0.01). Neither administration of dopamine (1 microgram/kg/min) nor long-term therapy with bromocriptine (2.5 mg t.i.d. for 4 weeks) affected aldosterone biosynthesis. Thus, loss of dopaminergic inhibition of mineralocorticoid biosynthesis does not account for hyperaldosteronism in this condition.(ABSTRACT TRUNCATED AT 250 WORDS)

Pilot study of the effects of the angiotensin-converting enzyme inhibitor CI-906 on patients with essential hypertension.

The effects of two single doses of the new oral nonsulfhydryl angiotensin-converting enzyme (ACE) inhibitor CI-906 on blood pressure and hormone levels are described in eight subjects with essential hypertension. Starting at 0.625 mg, doses were separated by a placebo day and doubled in consecutive patients until the full effect (obtained with 5 and 10 mg) was reached, at which point the remaining patients received the same dosage. All doses, including the smallest, caused ACE suppression to less than 1 per cent of baseline lasting for least 12 hours and remaining below 30 per cent at 48 hours, accompanied by a rise in plasma renin activity (by 10.9 +/- 2.1 ng/ml/hr) and fall in aldosterone (by -12.6 +/- 2.5 ng/100 ml). However, a clinically significant, though partial and short-lived, effect on blood pressure was observed at 2.5 mg. The two highest doses produced similar effects in terms of magnitude of mean blood pressure lowering (by 26 +/- 5 and 25 +/- 2 mm Hg, respectively) and duration (varying from 12 to over 24 hours) regardless of pretreatment renin levels. There was no orthostatic hypotension, tachycardia, or other adverse reaction.

A simultaneous radioimmunoassay for aldosterone and its precursors: human plasma levels following the inhibition of converting enzyme, before and after blockade of prostaglandin biosynthesis.

Plasma aldosterone, 18-hydroxycorticosterone, corticosterone, 18-hydroxydeoxycorticosterone, and deoxycorticosterone were determined in 15 healthy male volunteers (34 +/- 2 years) following the inhibition of converting enzyme with captopril (SQ 14.225), either with or without indomethacin pretreatment. These studies were performed with the aid of a radioimmunological method for the simultaneous determination of the steroids from 1.0 ml of plasma. The procedure involves one extraction and one chromatographic step. Highly sensitive and specific rabbit antisera were raised for all steroids. Precision and accuracy are shown to be equivalent to those of single steroid radioimmunoassays. Without indomethacin pretreatment a constant and significant fall in aldosterone and 18-hydroxycorticosterone plasma levels was obtained after captopril. 18-Hydroxydeoxycorticosterone and corticosterone did not change after inhibition of converting enzyme. Under indomethacin pretreatment all basal steroid levels were significantly reduced. After captopril, aldosterone did not change and 18-hydroxycorticosterone showed a smaller decrease than without indomethacin. 18-Hydroxydeoxycorticosterone and corticosterone increased significantly 1 1/2 hour after captopril. We conclude that indomethacin significantly reduces basal mineralocorticoid production of adrenal zona glomerulosa and fasciculata. Furthermore, the effect of captopril on aldosterone and 18-hydroxycorticosterone is abolished or diminished by inhibition of prostaglandin biosynthesis, but indomethacin does not prevent an augmented secretion of 18-hydroxydeoxycorticosterone and corticosterone.

Humoral and hormonal changes in menstrual migraine.

SYNOPSISCircadian plasma levels of aldosterone, renin activity, cortisol, sodium and potassium were studied during the migraine attack and headache‐free periods in ten women with menstrual migraine. Aldosterone dropped at the onset of an attack in all cases, producing an inverted profile when plotted at two‐hourly intervals over a 24‐hour period and compared with aldosterone levels during a headache‐free period. Renin activity and cortisol levels were normal during migraine and headache‐free periods and potassium and sodium were normal during the migraine attack. A possible explanation for the fall in aldosterone during the attack phase is increased conjugation in the liver due to increased hepatic blood flow.

The effects of saralasin, an angiotensin II antagonist, on blood pressure and the renin-angiotensin-aldosterone system in normal and hypertensive subjects.

Blood pressure reduction with saralasin infusion was seen only in hypertensive patients with abnormally elevated basal plasma renin and angiotensin II levels, and after sodium depletion the reduction in blood pressure was more marked. In normal subjects, and in hypertensives with plasma renin and angiotensin II levels within the normal range, there was no marked fall in blood pressure across saralasin infusion regardless of the sodium status of the individual. Plasma aldosterone concentration fell during saralasin infusion in those subjects with high baseline renin and angiotensin II levels. This fall occurred in the sodium replete and deplete states. In the normal subjects, and those hypertensives with normal plasma renin levels, there was no fall in aldosterone in the sodium replete state. However, after sodium depletion the expected rise in aldosterone was abolished during saralasin infusion, the plasma aldosterone falling to within the normal sodium replete range, rising again after the saralasin infusion was stopped. This study supports the concept of a direct role for renin and angiotensin II in the maintenance of hypertension in those subjects with elevated basal plasma renin. Plasma aldosterone would appear to be controlled, at least in part, by the prevailing plasma angiotensin II level in those subjects with elevated basal levels of angiotensin II; that is in high renin hypertensives, and in normal subjects and normal renin hypertensives who are sodium deplete.

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.

Studies of the control of plasma aldosterone concentration in normal man. I. Response to posture, acute and chronic volume depletion, and sodium loading.

The peripheral plasma levels of aldosterone, renin activity (PRA), potassium, corticosterone, cortisol, and in some cases angiotensin II, were measured in normal subjects undergoing postural changes, acute diuretic-induced volume depletion, and alterations in dietary sodium. On a 10 mEq sodium/100 mEq potassium intake, subjects supine for 3 consecutive days had identical diurnal patterns of PRA, angiotensin II, aldosterone, cortisol, and corticosterone, with peaks at 8 a.m. and nadirs at 11 p.m. With an increase in sodium intake to 200 mEq, plasma levels of aldosterone and PRA fell to one-third their previous levels but the diurnal pattern in supine subjects was unchanged and again parallel to that of cortisol and corticosterone. There was no diurnal variation of plasma potassium on either sodium intake in the supine subjects. On a 10 mEq sodium/100 mEq potassium intake, supine 8 a.m. plasma aldosterone (55+/-7 ng/100 ml) and PRA (886+/-121 ng/100 ml per 3 hr) increased by 150-200% after subjects were upright for 3 hr. However, even though the patients maintained an upright activity pattern, there was a significant fall in plasma aldosterone to 33+/-5 ng/100 ml at 11 p.m. Potassium levels varied in a fashion parallel to aldosterone and PRA. Plasma cortisol and corticosterone had a diurnal pattern similar to that found in supine subjects. In response to acute diuretic-induced volume depletion, the nocturnal fall in aldosterone levels did not occur. The 11 p.m. value (102+/-20 ng/100 ml) and the 8 a.m. value postdiuresis (86+/-15 ng/100 ml) were both significantly greater than the prediuresis levels. PRA showed a similar altered pattern while potassium levels fell throughout the day. In some but not all studies, changes in plasma aldosterone coincided with changes in plasma cortisol, corticosterone, and/or potassium. However, in all studies, changes in plasma aldosterone were invariably associated with parallel changes in plasma renin activity and/or angiotensin II levels. These findings support the concept that PRA is the dominant factor in the control of aldosterone when volume and/or dietary sodium is altered in normal man.