The classic mode of action of aldosterone involves nuclear transcription and synthesis of aldosterone-induced proteins over a period of hours to days. However, there is growing evidence to suggest that aldosterone, like other steroid hormones, may exert rapid effects via non-genomic mechanisms over a period of minutes. These rapid effects have been studied in a number of cell types, but there is little information about aldosterone’s action on its major target site, the renal epithelium. In vitro studies have shown that aldosterone stimulates Na⁺-H⁺ exchange in MDCK cells within 2-4 min, via an intracellular Ca²⁺-mediated mechanism (Gekle et al. 1997), but it is not known whether these effects are seen in vivo. Accordingly, the aim of this study was to determine whether aldosterone stimulates rapid changes in renal sodium excretion in vivo.

Under Intraval anaesthesia (100 mg kg^-1 sodium thiopentone) male Sprague-Dawley rats received euvolaemic fluid replacement (2.5% dextrose, [³H] inulin) of spontaneous urine output using a servo-controlled system (Burgess et al. 1993). After a 3 h equilibration period, control urine and plasma samples were taken for 1 h, following which half of the animals received aldosterone (42 pmol min^-1) for 1 h before returning to dextrose alone for the final hour. Animals were humanely killed at the end of the experiment.

Blood pressure (vehicle, n = 8, 90 ± 1 vs. aldosterone, n = 10, 103 ± 1 mmHg, means ± S.E.M.) and glomerular filtration rate (vehicle 0.70 ± 0.05 vs. aldosterone 0.81 ± 0.03 ml min^-1 (100 g body wt)^-1) remained steady throughout the experiment. Urine flow rate (vehicle 15.1 ± 0.5 vs. aldosterone 15.4 ± 0.7 ml min^-1 (100 g body wt)^-1 over hour of treatment, ANOVA, P < 0.001) and sodium excretion (Fig. 1) increased significantly during the period of aldosterone infusion.

These changes were apparent within 15 min of the commencement of aldosterone infusion and had an equally rapid offset at the end of aldosterone infusion. The change in the sodium excretion rate from the control hour to aldosterone infusion hour was -12.9 ± 11.9% in vehicle infused rats compared with 404.7 ± 256.7 % in aldosterone infused rats (Mann-Whitney U test, P < 0.01). Potassium and osmolar excretion were not affected by aldosterone infusion.

These data show that aldosterone is able to induce a rapid increase in urinary sodium but not potassium excretion in vivo. This contrasts with its classic mode of action in which sodium excretion falls and potassium excretion increases over a period of hours to days. The mechanisms involved in this rapid response to aldosterone are unclear at this stage, but probably involve a non-genomic pathway.

Figure 1. Urinary sodium excretion in vehicle (2.5% dextrose, n = 8) and aldosterone (42 pmol min-1, n = 10) treated rats.

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