Sex-dependence of the metabolism of aldosterone in adrenalectomized and intact rats

The metabolism of aldosterone at physiological levels was shown to be significantly different in male and female rats: more aldosterone was metabolized in the male rats leading to significantly higher quantities of non-extractable polar derivatives of aldosterone in all subcellular fractions of kidney, particularly in the cytosol fractions. These results may be correlated with our findings in which it was shown that the physiological responses to aldosterone in both adrenalectomized and intact rats were significantly greater in the males than the females. These sex differences support the concept that the metabolism of aidosterone may be essential for the components of the physiological response to aldosterone to occur. Furthermore, the sex-dependence of the metabolism of aldosterone appears to be independent of the presence of the previously identified protein receptor-hormone complexes. At all dosages within the physiological range, no significant differences were observed between the extent of the ³H-aldosterone labeling of these binding proteins in the kidney cytosol fractions of male and female adrenalectomized rats, even at dosages where no physiological response was demonstrable in the females.     

Reduced urinary aldosterone excretion rates with normal plasma concentrations of aldosterone in the very elderly

Although aldosterone production declines with age, so does the aldosterone metabolic clearance rate (MCR), and the net effect of age on the circulating level of aldosterone may be less than can be predicted from production rates alone. The effect of age on aldosterone production and plasma levels was studied in a group of elderly individuals at a very advanced age when susceptibility to the impacts of age might be particularly pronounced. Seventeen nursing home patients, ages 75-99 (mean age 86 years), had aldosterone production assessed from the urinary excretion rate of the acid hydrolyzable 18-glucuronide conjugate of aldosterone. Aldosterone excretion was low in the elderly when compared to a group of healthy, young to middle-aged subjects: 123 +/- 19 (SEM) vs. 234 +/- 18 ng/h (P less than 0.001). However, plasma aldosterone concentrations in the elderly were well within a range observed in much younger and fully ambulatory subjects: 14.1 +/- 1.3 in the elderly vs. 15.9 +/- 1.8 ng/dL in the young. The plasma aldosterone concentration was apparently maintained at a normal level by a coincident decrease in both the metabolic clearance rate and the aldosterone production rate. In conclusion, an aldosterone deficiency state resulting from an age-correlated reduction in aldosterone production is probably uncommon in the elderly.     

Effects of acute intravenous aldosterone administration on Na(+), K(+), and water excretion in the horse.

The effect of a temporary increase in plasma aldosterone concentration on Na(+), K(+), and water balance was investigated in four horses. Aldosterone was injected intravenously for 6 h at 20-min intervals (total 5.4 microg/kg body wt). Samples were taken for 24 h before, during, and for 48 h after the treatment. Aldosterone treatment reduced the Na(+) loss via urine and feces by 99 and 72%, respectively, later followed by a marked increase in Na(+) excretion by both pathways. During the first 6 h after the treatment, fecal K(+) excretion was elevated, and the plasma K(+) concentration was lowered. Fluid was retained throughout the treatment period and for 12-15 h thereafter. In a second experiment, exercise was performed once after aldosterone treatment and once without prior treatment. Sweat samples were collected, and the composition was not altered after treatment. It was concluded that acute aldosterone injections reduce Na(+) losses in both feces and urine but not in sweat. In addition, the feces was shown to be the main excretion pathway of aldosterone.     

The hypothalamic and neurohypophysial vasopressin and oxytocin content under various states of adrenergic transmission in dehydrated and subsequently rehydrated rats

Rats dehydrated for 8 days and subsequently rehydrated were given intracerebroventricularly (i.c.v.) methoxamine hydrochloride (MX) or dihydroergotamine methanosulphonate (DHE), each in a daily dose of 10 micrograms dissolved in 10 microliter of 0.9% sodium chloride. A single dose of MX injected to normally hydrated animals increased the release of hypothalamic and neurohypophysial vasopressin but did not affect significantly the oxytocic activity in the hypothalamus as well as in the neurohypophysis. Under conditions of dehydration MX did not influence the hypothalamic vasopressin content but it stimulated the neurohypophysial vasopressin depletion. On the contrary, MX distinctly inhibited the decrease of hypothalamic and neurohypophysial oxytocin content in dehydrated animals. In rehydrated animals MX restrained some what the renewal of hypothalamic vasopressin and oxytocin storage but intensified this process in the neurohypophysis. A single dose of DHE decreased the vasopressin content in the hypothalamus as well as the oxytocin content both in the hypothalamus and neurohypophysis. Under conditions of dehydration DHE stimulated the depletion of hypothalamic vasopressin and oxytocin. On the contrary, DHE strongly inhibited the depletion of oxytocin in the neurohypophysis of dehydrated rats. DHE restrained the renewal of hypothalamic vasopressin and oxytocin stores as well as intensified this process in the neurohypophysis of subsequently rehydrated rats.     

Urinary excretion of aldosterone metabolite Kelly-M1 in patients with adrenal dysfunction

Using tetrahydroaldosterone antibody a radioimmunoassay was developed to measure substance Kelly-M1 (K-M1) in human urine. The normal values were lower than observed by Kelly et al. who discovered the catabolite after giving large doses of exogenous aldosterone. While in essential hypertension the excretion of K-M1 was predominantly within the normal range, elevated values were found in most cases of 21-hydroxylase deficiency, both the simple virilizing and salt losing form, primary aldosteronism, renal hypertension and cystinosis. Our findings suggest that K-M1 may be formed from 21-deoxyaldosterone and/or by microbial intervention from aldosterone or its metabolites.     

Antagonistic effects of aldosterone on corticosterone-mediated changes in exploratory behavior of adrenalectomized rats

The effect of aldosterone administration on exploratory activity of chronic adrenalectomized (10 days) male rats was investigated. Aldosterone (30 μg/100 g body wt sc) administered 1 hr or 30 min prior to the behavioral test failed to normalize disturbed exploratory activity of adrenalectomized rats, in contrast to the restoration observed after corticosterone, the naturally occurring glucocorticoid of the rat. Administration of the mineralocorticoid 30 min prior to corticosterone prevented the normalization of the behavioral response by the latter steroid. Administration of the same dose of aldosterone 30 min prior to a tracer amount of [³H]corticosterone effectively blocked cell nuclear uptake of radioactive-labeled hormone in the hippocampus. The specific action of corticosterone on exploratory behavior corresponds with the stringent specificity of the neuronal hippocampal corticosterone receptor system. Mineralocorticoid receptors do not seem to be involved in effects on this behavior. The antagonistic action of aldosterone is probably exerted by competitive binding to the corticosterone receptor.