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. Continous 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.

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 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 pento-barbital anesthetized. An acute intravenous injection of 1 µg rat CRH/100g 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.

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.

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 0.40μg/l00g 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.