Glucocorticoids Inhibit Sodium Depletion-induced Salt Appetite in Rat

Glucocorticoids, produced in adrenal cortex, exert potent natriuretic and diuretic actions in the kidney. Recently, it has been found that glucocorticoids could upregulate the expression of natriuretic peptide receptor A (NPR-A), the primary receptor of atrial natriuretic peptide, in the hypothalamus of the rat. Consequently, systemic administration of glucocorticoid could block dehydration-induced water intake by activation hypothalamic NPR-A. We describe here glucocorticoids could inhibit sodium intake when administrated systemically in conscious, salt-depleted rats; an effect which was strong and long-lasting. The study provided further evidence for the actions of glucocorticoids on central nervous system, which together with their established renal actions coordinated to normalize extracellular fluid volume

Inhibition of Dehydration-Induced Water Intake by Glucocorticoids Is Associated with Activation of Hypothalamic Natriuretic Peptide Receptor-A in Rat

Atrial natriuretic peptide (ANP) provides a potent defense mechanism against volume overload in mammals. Its primary receptor, natriuretic peptide receptor-A (NPR-A), is localized mostly in the kidney, but also is found in hypothalamic areas involved in body fluid volume regulation. Acute glucocorticoid administration produces potent diuresis and natriuresis, possibly by acting in the renal natriuretic peptide system. However, chronic glucocorticoid administration attenuates renal water and sodium excretion. The precise mechanism underlying this paradoxical phenomenon is unclear. We assume that chronic glucocorticoid administration may activate natriuretic peptide system in hypothalamus, and cause volume depletion by inhibiting dehydration-induced water intake. Volume depletion, in turn, compromises renal water excretion. To test this postulation, we determined the effect of dexamethasone on dehydration-induced water intake and assessed the expression of NPR-A in the hypothalamus. The rats were deprived of water for 24 hours to have dehydrated status. Prior to free access to water, the water-deprived rats were pretreated with dexamethasone or vehicle. Urinary volume and water intake were monitored. We found that dexamethasone pretreatment not only produced potent diuresis, but dramatically inhibited the dehydration-induced water intake. Western blotting analysis showed the expression of NPR-A in the hypothalamus was dramatically upregulated by dexamethasone. Consequently, cyclic guanosine monophosphate (the second messenger for the ANP) content in the hypothalamus was remarkably increased. The inhibitory effect of dexamethasone on water intake presented in a time- and dose-dependent manner, which emerged at least after 18-hour dexamethasone pretreatment. This effect was glucocorticoid receptor (GR) mediated and was abolished by GR antagonist RU486. These results indicated a possible physiologic role for glucocorticoids in the hypothalamic control of water intake and revealed that the glucocorticoids can act centrally, as well as peripherally, to assist in the normalization of extracellular fluid volume

The effect of Dex pretreatment on plasma ANP and hypothalamic ANP content in the water-deprived rats.

<p>[<b>A</b>] Effect of 6-hour Dex pretreatment on plasma ANP levels in water-deprived rats; *<0.01 compared with rats treated with vehicle; # <0.01 compared with rats treated with low dose of Dex. [<b>B</b>] Effect of 24-hour Dex pretreatment on plasma ANP levels in water-deprived rats; *<0.01 compared with rats treated with vehicle; # <0.01 compared with rats treated with low dose of Dex. [<b>C</b>] Effect of 24-hour Dex pretreatment on hypothalamic ANP contents in water-deprived rats; n = 10 for each group.</p

The effect of 6-hour Dex pretreatment on urinary volume and water intake.

<p>[<b>A</b>] Effect of Dex pretreatment on urinary volume during 6-hour pretreatment period; *<0.01 compared with rats treated with vehicle. [<b>B</b>] Effect of Dex pretreatment on cumulative water intake during water-access period in the dehydrated rats; n = 10 for each group; data were analyzed by two-way repeated measures ANOVA. [<b>C</b>] Effect of Dex pretreatment on urinary volume during water-access period; *<0.01 compared with rats treated with vehicle; # <0.01 compared with rats treated with low dose of Dex.</p