Effect of aging and sodium deprivation on plasma concentration of aldosterone and on plasma renin activity in the rat.

Age-related changes in plasma aldosterone and corticosterone concentrations as well as in plasma renin activity in response to 10 days of sodium deprivation were studied in old as compared to adult male Long-Evans rats. Chronic sodium deprivation greatly increased plasma concentrations of aldosterone both in old and in adult animals. However, this effect was significantly higher (+85.2%) in old (+3,574 pmol/l) as compared to adult (+1,820 pmol/l) rats. Concomitantly, adrenal weights were statistically increased in sodium-deprived old rats (+25%) whereas they were unchanged in adult animals; plasma corticosterone concentration was unchanged by sodium restriction in the two age groups. Because a putative modest decline with age of the metabolic clearance rate of aldosterone could not account totally for such an important increase in plasma concentration, it is assumed that it is, in its most part, due to an increased production. Furthermore, although plasma renin activity of senescent rats, fed either a normal or a sodium-deprived diet, was lower as compared to adult rats, the absolute and percent increases of this activity in response to sodium deprivation were, respectively, similar and higher in old as compared to adult rats and so could partially contribute to the higher aldosterone response.

Age-related changes in secretion and metabolic effects of a trial natriuretic factor in rats.

The effects of aging on the secretion of and renal sensitivity to atrial natriuretic factor (ANF) were studied concomitantly in both senescent (25- to 34-month-old) and in adult (7- to 13 month-old) female and male Long-Evans rats. The plasma concentrations of ANF, measured in response to either a mild stimulation induced by a hypertonic volume expansion (i.e., 20 min after the onset of a continuous infusion during 15 min of a 2.5% NaCl solution; n = 18 old and 23 adult rats) or an intense stimulation produced by morphine injection (i.e., 30 min after an intraperitoneal injection of 5 mg morphine/100 g body weight; n = 11 old and 12 adult rats), were significantly lower (approximately -34 and -80%, respectively) in old as compared with adult animals. Acute intravenous injection of exogenous rat ANF (0.10 and 0.40 mu g/100 g body weight) induced similar natriuretic, diuretic, and kaliuretic effects in aged (n = 18) and in adult (n = 23) rats. The present data suggest that the significantly reduced (about -20%) natriuretic and kaliuretic responses of the aged rat, observed 20 min after the onset of hypertonic volume expansion, could be partly due to a primary defect in cardiac production and/or release of ANF rather than to a reduction of renal responsivity to ANF.

Age-related changes in plasma corticosterone and aldosterone responses to exogenous ACTH in the rat.

Age related changes in the time courses of response of plasma corticosterone and aldosterone to exogenously applied ACTH were simultaneously studied in old (female and male) Long-Evans rats and compared to both young and adult pentobarbitone-anesthetized and dexamethasone-pretreated control rats. Acute intravenous injection of either 0.5 or 50.0 ng ACTH (1-24)/100 g body weight increased plasma concentrations of the two steroids with a similar time course in all groups of rats. However, we observed a significant age-related attenuation in the plasma corticosteroid response. Thus, in old as compared to young rats there was a decrease of approximately 45, 40 and 30% in plasma corticosterone levels respectively 8 min after the lower dose of ACTH in female and 45 min after the higher dose in female and male rats. Similarly, an attenuated (approximately -38%) response of plasma aldosterone levels, induced 45 min after the higher dose of ACTH, was observed both in old female and male rats. These results suggest that the previously reported age-related decreases of in vivo corticosterone and aldosterone secretion are, at least in part, due to a reduced capacity of adrenocortical cells for steroid biosynthesis and release in response to stimulation by ACTH.

Age-related decreases in plasma adrenocorticotropic hormone, corticosterone, and aldosterone responses to exogenous corticotropin-releasing hormone in the rat.

Age-related changes in plasma adrenocorticotropic hormone (ACTH), corticosterone, and aldosterone responses to exogenous corticotropin-releasing hormone (CRH) were studied concomitantly in both old and adult Long-Evans female rats. All animals were pretreated with dexamethasone and pentobarbital anesthetized. An acute intravenous injection of 1 micrograms rat CRH/100 g body weight markedly increased the plasma concentrations of ACTH, corticosterone, and aldosterone--with similar temporal kinetics in the two groups of rats. However, the incremental CRH responses were significantly lower in old (approximately -70, -45-60, and -30-50%, respectively, for ACTH, corticosterone, and aldosterone) as compared with adult rats. Together with our recent findings, the present results suggest that the previously reported reduced secretion of corticosteroids in aged rats is due to both an impaired steroidogenetic capacity of adrenocortical cells to respond to ACTH and to a decreased ability of corticotropes to produce ACTH in response to CRH.

Seasonal changes in in vivo cortisol response to ACTH and in plasma and pituitary concentrations of ACTH in a desert rodent, the sand rat (Psammomys obesus).

1. During spring, decreased sensitivity of the adrenal cortex to adrenocorticotrophic hormone (ACTH) in the sand rat inhabiting the Béni-Abbès area (Algeria), results in a reduction in the production of cortisol. Thus the secretion of ACTH is enhanced, becoming maximal in June and presumably also during the following weeks. 2. Increase in ACTH secretion, together with a slightly increased adrenal sensitivity, is likely to stimulate corticosteroidogenesis throughout the summer. 3. In autumn, as levels of cortisol are high, the negative feedback increases leading to a reduction in ACTH production. 4. An increase in the adrenocortical sensitivity to ACTH allows a high production of cortisol until February.

Age-related change in plasma aldosterone response to exogenous angiotensin II in the rat.

Age-related changes in aldosterone response of the adrenal cortex to exogenous angiotensin II were studied in old compared to adult Long-Evans female rats. All animals were pretreated with dexamethasone and captopril and anesthetized with pentobarbital. Continuous infusion of angiotensin II (20 and 300 ng/min per 100 g body weight) for 20 and 30 min markedly enhanced the plasma concentration of aldosterone; however, the plasma aldosterone incremental response was significantly lower (-66.8% after the highest dose of angiotensin II) in old than in adult rats. These results, the first in the rat, suggest that the previously reported diminished aldosterone secretion is, at least in part, due to an impaired aldosterone biosynthesis capacity of the adrenal glomerular cells in response to angiotensin II.

Seasonal changes in plasma concentrations of gonadotropins and in the responsiveness of the pituitary and testis to GnRH in a desert rodent, the sand rat (Psammomys obesus).

The male sand rat (Psammomys obesus), captured alive in the Sahara desert in the area of Béni-Abbès (Algeria), exhibited seasonal changes in plasma concentrations of LH, characterized by an increase in early summer. Administration of a standard dose of GnRH (200 ng/100 g body weight) failed to elicit significant season-dependent changes in LH release, whereas the increase in plasma testosterone was maximum in June-July and quite small between November and March-April. The present results suggest that the summer seasonal onset of the testicular endocrine activity of the sand rat is due to increases both in LH release and in testis sensitivity to gonadotropin.

Effect of sodium deprivation on plasma and adrenal concentrations of aldosterone and corticosterone in the Brattleboro homozygous rat.

Despite the great impairment in water balance occurring in the Brattleboro rat, homozygous for diabetes insipidus and lacking hypothalamic arginine-vasopressin, fed a normal sodium diet, the metabolic effects of a chronic sodium deprivation were similar in the Brattleboro rat and in the Long-Evans rat used as control. Concomitantly, whilst the plasma and adrenal concentrations of aldosterone were two fold lower in the Brattleboro rat than in the Long-Evans rat fed a normal diet, after ten days of sodium restriction they became similar in the two groups of rats; sodium deprivation greatly increased aldosterone production in the same order of magnitude both in the Brattleboro rat and in the Long-Evans rat. It is suggested that chronic sodium depletion might have, in the Brattleboro rat, either suppressed the cause of the reduced aldosterone secretion or induced mechanisms which have offset it.

Atrial natriuretic factor is unlikely to be involved in the reduced aldosterone production in the Brattleboro rat.

We have previously reported that basal and stimulated aldosterone production in Brattleboro rat (DI) lacking hypothalamic arginine vasopressin is lower than that observed in control Long-Evans rat (LE). In the present study, we investigated the secretion under various experimental conditions, adrenal binding sites, and the aldosterone-inhibiting effect of atrial natriuretic factor (ANF). In the conscious resting state, the plasma ANF concentration was similar between LE and DI rats. Pentobarbital anaesthesia (5 mg/100 g body wt.) reduced the plasma ANF concentration equally in both groups, with or without captopril pretreatment. Morphine (10 mg/100 g body wt.) increased ANF secretion dramatically and equally in the two groups of pentobarbital anaesthetized (2 mg/100 g body wt.) rats. In dexamethasone pretreated-pentobarbital anaesthetized rats, a concurrent i.v. ANF infusion (50 ng/min) did not change significantly the corticosterone response to ACTH (1-24) (1 mI.U./100 g body wt.) but steeply depressed ACTH-induced aldosterone production to a similar extent between DI and LE rats. A single class of adrenal ANF receptor sites was found with a similarity in high affinity and maximum binding capacity between the two groups of rats. Taken together, these results suggest that the reduced aldosterone production by Brattleboro rat adrenals is unlikely to be related to the inhibitory effect of ANF.

Seasonal changes in plasma testosterone concentrations in response to administration of hCG in a desert rodent, the sand rat (Psammomys obesus).

In adult male sand rats inhabiting the Béni-Abbès area (Algeria), testicular endocrine activity increased in early summer (June-July), was highest in autumn-winter and decreased throughout spring. Testosterone secretion by the testis of the sand rat was stimulated (by 10-60-fold) throughout the year by exogenously administered hCG (25 i.u.). However, the response exhibited annual changes mainly characterized by a marked increase in early summer (June-July); the response to hCG was depressed in autumn and became minimal in winter and in early spring. The results strongly suggest that the summer onset of testicular endocrine activity is, at least in part, due to an increase in the testis sensitivity to LH.

Aldosterone secretion and adrenal angiotensin II receptors in the Brattleboro rat.

The basal secretion of aldosterone, measured in adrenal venous blood, was three- to fourfold lower in Brattleboro than in Long-Evans rats used as controls. Infusion of a low dose of angiotensin II (1 ng/min per 100 g body/wt) to Long-Evans rats caused a fourfold increase in aldosterone release but neither the low dose nor a tenfold higher dose changed the rate of release in Brattleboro rats. Only a very high dose (300 ng/min per 100 g body wt) succeeded in increasing the secretion of aldosterone in Brattleboro rats but throughout the time-course of the infusion, secretion remained about fivefold lower than in Long-Evans rats and the incremental response was reduced by 74.9%. Adrenal zona glomerulosa angiotensin II receptor sites had similar affinity and maximum binding capacity in the two groups of rats. It is suggested that the reduced corticosteroidogenic capacity of the adrenal cortex of Brattleboro rats results from an impairment of the post-receptor mechanisms involved in the biosynthesis of aldosterone.

Seasonal changes in testicular contents and plasma concentrations of androgens in the desert gerbil (Gerbillus gerbillus).

Gerbils were caught in the Béni-Abbès area (Algeria). Testicular endocrine activity was highest in spring (testicular wt 298 +/- 10 mg; seminal vesicle wt 603 +/- 62 mg; testicular testosterone and androstenedione content 9.2 +/- 1.7 and 0.5 +/- 0.1 ng/testis; plasma testosterone 832 +/- 200 pg/ml). Values decreased in summer, were lowest in late summer and in autumn (84 +/- 17 mg; 40 +/- 14 mg; 0.20 +/- 0.06 and 0.02 +/- 0.01 ng/testis; 228 +/- 54 pg/ml, respectively) and increased again in winter (December-January). The onset of testicular endocrine activity was concomitant with the lowest temperatures and the shortest photoperiod; it increased when temperatures and daylength were increasing and began to decline when temperatures and photoperiod were still maximal. These seasonal changes in the endocrine activity of the testis of the gerbil differ from those of the sand rat inhabiting the same area.

Release of aldosterone and corticosterone from the adrenal cortex of the Brattleboro rat in response to administration of ACTH.

The time-course and dose-response of the in-vivo secretion of aldosterone and corticosterone after administration of ACTH(1-24) were measured in adrenal venous blood from female Brattleboro rats, homozygous for hypothalamic diabetes insipidus and lacking arginine vasopressin (AVP). Female Long-Evans rats were used as controls. All animals were pretreated with dexamethasone and anaesthetized with pentobarbital. Basal secretions of aldosterone and corticosterone were four- to sixfold lower in Brattleboro than in Long-Evans rats. Administration of ACTH consistently increased the secretion of aldosterone and corticosterone similarly in the two groups of rats; maximum values were observed 20-30 min after ACTH injection. However, for all the doses of ACTH (0.05, 0.5 and 5.0 mi.u./100 g body wt) and at every stage of response the secretion rates of aldosterone and corticosterone were twofold lower in Brattleboro than in Long-Evans rats. Furthermore the absolute increase in steroid secretion induced by ACTH was reduced by half in Brattleboro rats. These results show that the impairment of adrenal activity is largely due to a reduced capacity for corticosteroidogenesis in the adrenal cortex of Brattleboro rats. The mechanisms of action of AVP are discussed.

Production of corticosterone in male homozygous Brattleboro rats.

Plasma concentration, metabolic clearance rate and in vitro adrenal production of corticosterone were measured in Brattleboro male rats homozygous for diabetes insipidus (DI) and in Long-Evans male rats (LE) as controls in resting conditions, under stress caused by pentobarbitone anesthesia and surgery and after three days water deprivation. In resting animals, plasma concentrations and in vitro adrenal production of corticosterone were higher in DI rats than in LE rats. Under pentobarbitone anesthesia and surgery, plasma concentrations and metabolic clearance rate of corticosterone were slightly but not statistically lower in DI rats; however, the in vivo production rate of corticosterone was significantly lower. After three days water deprivation, increasing plasma corticosterone level was consistently higher in DI than in Le rats. These results are not in favour of a reduced glucocorticoid activity of the adrenal of DI rats and of an important role played by vasopressin on the stimulation of the hypothalamopituitary adrenal activity at least in resting conditions; its role may depend upon stressful circumstances.

Effects of water-deprivation on aldosterone production in Brattleboro male rats congenitally lacking vasopressin.

Effects of water-deprivation on several metabolic parameters and on plasma aldosterone concentration have been investigated in male Brattleboro rats homozygous for hypothalamic diabetes insipidus (DI) and in male Long-Evans rats (LE) as controls. Two separate experiments were performed over a period of 72 hours: 1) to determine the global effect of water-deprivation, water deprived rats were compared with hydrated animals, 2) to elucidate the specific effect of dehydration alone, water-deprived rats were compared with similar food-restricted, but water-supplied DI and LE rats. In hydrated animals, plasma aldosterone concentration was close to 50% less in DI rats than in LE rats. After 72 hours, plasma aldosterone values increased mainly because of dehydration and this increase was greater in DI rats than in LE rats. At the same time, plasma aldosterone concentration remained lower in DI rats compared to LE rats. The changes in plasma aldosterone concentration after dehydration and possible reasons for the impairment of aldosterone production in DI rats are discussed.

[Effects of water deprivation on corticosterone production in the male Brattleboro rat genetically deprived of vasopressin]. / Effets de la privation d'eau sur la production de corticostérone chez le rat mâle Brattleboro génétiquement privé de vasopressine.

Effects of 72 h water-deprivation on plasma corticosterone concentration have been investigated in male Brattleboro rats homozygous for hypothalamic diabetes insipidus (DI) and in male Long-Evans rats (LE), as controls. To determine the global effect of water deprivation, drinking water deprived rats were compared with hydrated animals. Because water deprived rats showed a depressed food intake, to elucidate the specific effect of dehydration alone, drinking water deprived rats were compared with similar food-restricted but water supplied animals. Increases in adrenal weights and in plasma corticosterone content, following 72 h water-deprivation, were greater in DI than in LE rats. In LE rats, they seemed to be the result of both dehydration and denutrition. Conversely in DI rats lacking vasopressin, dehydration alone increased neither adrenal weights nor plasma concentration of corticosterone; the whole plasma corticosterone content was reduced. So, in DI rats, the global response to drinking water deprivation was essentially due to food restriction, whose effect was partly suppressed by dehydration. Whatever the circumstances, plasma concentrations of corticosterone were higher in DI than in LE rats. Interrelationships between water deprivation, stress, vasopressin and glucocorticoids are discussed.

Seasonal changes in testicular contents of testosterone and androstenedione and in the metabolic clearance rate of testosterone in the sand rat (Psammomys obesus).

Adult male sand rats (Psammomys obesus) were caught in the Béni-Abbès area. The highest testicular contents of androgens (ng/testis) were observed in autumn and in winter (testosterone: 7.6 +/- 1.1; androstenedione: 0.76 +/- 0.11) and the lowest in early summer (June) (testosterone: 1.5 +/- 0.3; androstenedione: 0.20 +/- 0.05). Values had increased by late July. Annual variations of the testosterone metabolic clearance rate (litres/24 h/100 g body wt) were similar to those of testicular androgens; values were high in winter (6.7 +/- 0.7) and lowest in June (3.2 +/- 0.3). The onset of testicular endocrine activity in sand rats was concomitant both with the highest temperatures and the start of reduction in photoperiod; its regression occurred when temperature and photoperiod were increasing.

Production of aldosterone in male rats with inherited diabetes insipidus (Brattleboro strain).

Plasma concentration, metabolic clearance rate and in vitro adrenal production of aldosterone were measured in Brattleboro male rats with inherited diabetes insipidus (DI) and in Long-Evans male rats (LE) as controls. Plasma concentration of aldosterone was significantly lower (-48.3%) in DI rats than in LE rats. Metabolic clearance rate of aldosterone was not statistically different between Brattleboro and Long-Evans rats, suggesting that the in vivo production rate of aldosterone was reduced by half in DI rats. Conversely, the basal in vitro production of aldosterone by adrenal tissue was similar in the two groups of rats. The reason for impairment of the in vivo production of aldosterone by Brattleboro rats congenitally lacking vasopressin is discussed. It is suggested that despite possibly indirect influence on the factors involved in the control of aldosterone secretion, mainly ACTH and potassium, vasopressin effects might occur in situ on the adrenal glomerulosa cells.

Seasonal changes in the metabolic clearance rate of cortisol in the adult male sand rat (Psammomys obesus).

Metabolic clearance rate (MCR) of cortisol was measured in the adult male sand rat (Psammomys obesus) trapped live throughout the year in the region of Béni-Abbès in the Algerian Sahara Desert. Cortisol MCR exhibited marked annual variations which paralleled those of plasma concentrations of cortisol: it was highest in autumn, decreased in winter, rose again in early March, and was minimal in April and June. These data, taken together with previous results, suggest that the production rate of cortisol in the sand rat is lower in early summer than in autumn.

[Secretion of aldosterone and corticosterone by the adrenals of Brattleboro rats in response to ACTH administration]. / Sécrétions d'aldostérone et de corticostérone par la surrénale du Rat Brattleboro en réponse à l'administration d'ACTH.

The secretions of aldosterone and corticosterone in response to administration of 0,5 mUI of (1,24) ACTH (synacthène-Ciba) were measured in the adrenal venous blood of 15 Brattleboro female rats genetically lacking vasopressin and in 15 Long-Evans female rats, pretreated with dexamethasone. The secretions of aldosterone and corticosterone increased according to a similar profile in the two groups of animals: maximum values were 20-30 min. after ACTH injection; however the steroidogenic secretion of the adrenal cortex was always about 50% less in the Brattleboro female rats than in Long-Evans female rats. This result suggests mainly that vasopressin may be involved in the mechanisms which control the in vivo production of aldosterone by the adrenal glomerulosa cells.