Glucocorticoids increase salt appetite by promoting water and sodium excretion

Abstract

Glucocorticoids [e.g., corticosterone and dexamethasone (Dex)], when administered systemically, greatly increase water drinking elicited by angiotensin and sodium ingestion in response to mineralocorticoids [e.g., aldosterone and deoxycorticosterone acetate (DOCA)], possibly by acting in the brain. In addition, glucocorticoids exert powerful renal actions that could influence water and sodium ingestion by promoting their excretion. To test this, we determined water and sodium intakes, excretions, and balances during injections of Dex and DOCA and their coadministration (DOCA+Dex) at doses commonly employed to stimulate ingestion of water and sodium. In animals having only water to drink, Dex treatment greatly increased water and sodium excretion without affecting water intake, thereby producing negative water and sodium balances. Similar results were observed when Dex was administered together with DOCA. In animals having water and saline solution (0.3 M NaCl) to drink, Dex treatment increased water and sodium excretion, had minimal effects on water and sodium intakes, and was associated with negative water and sodium balances. DOCA treatment progressively increased sodium ingestion, and both water and sodium intakes exceeded their urinary excretion, resulting in positive water and sodium balances. The combination of DOCA+Dex stimulated rapid, large increases in sodium ingestion and positive sodium balances. However, water excretion outpaced total fluid intake, resulting in large, negative water balances. Plasma volume increased during DOCA treatment and did not change during treatment with Dex or DOCA+Dex. We conclude that increased urinary excretion, especially of water, during glucocorticoid treatment may explain the increased ingestion of water and sodium that occurs during coadministration with mineralocorticoids.

Fig. 1

Body weight, cumulative sodium and potassium excretions, urine volume, water balance, and water intake for 24 h after injections of vehicle (Veh) or dexamethasone (Dex) in rats. Values are means ± SE. *Significantly different from Veh, P < 0.05.

Fig. 2

Body weight, cumulative sodium and potassium excretions, urine volume, water balance, and water intake for 24 h after injections of deoxycorticosterone acetate (DOCA), Dex, or their combination [DOCA+Dex (“both”)] in rats. Values are means ± SE. *Significantly different from DOCA, P < 0.01. #Significantly different from DOCA+Dex (both), P < 0.05.

Fig. 3

Daily total fluid intake, urine volume, water balance (Wat bal), and change in body weight (ΔBW) during treatment with DOCA, Dex, or DOCA+Dex (both). The average water balance over 4 days of baseline was used as the estimate of relative zero balance for each animal. Total fluid intake = water + saline. Values are means ± SE. *Significantly different from baseline, P < 0.05. #Significantly different from baseline and DOCA treatment, P < 0.05.

Fig. 4

Daily sodium intake, excretion, and balance and daily food intake during treatment with DOCA, Dex, DOCA+Dex (both). The average sodium balance over 4 days of baseline was used as the estimate of relative zero balance for each animal. Values are means ± SE. *Significantly different from baseline average, P < 0.05. #Significantly different from baseline and from DOCA treatment, P < 0.05.

Fig. 5

Cumulative sodium and water balance and cumulative body weight change during treatment with DOCA, Dex, DOCA+Dex (both). Values are means ± SE. *Significantly different from baseline, P < 0.05. #Significantly different from baseline and from DOCA treatment, P < 0.05.

Fig. 6

Daily 0.3 M NaCl and water intake, change in hematocrit, and cumulative change in body weight during treatment with DOCA, Dex, or DOCA+Dex (both). Values are means ± SE. *Significantly different from baseline, P < 0.01. #Significantly different from baseline and from DOCA, P < 0.01.