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 (DOCAϩDex) 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 DOCAϩDex 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 DOCAϩDex. 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. thirst; urine volume; dexamethasone; deoxycorticosterone acetate; food intake SYSTEMICALLY ADMINISTERED mineralocorticoids, such as aldosterone and deoxycorticosterone acetate (DOCA), stimulate vigorous sodium ingestion by activating mineralocorticoid receptors in the brain. Glucocorticoids, such as corticosterone, greatly increase this salt appetite response when coadministered with mineralocorticoids (2,17,33,35). Systemically administered glucocorticoids also increase water drinking in response to peripheral and central administration of ANG II (9, 27). The potentiation of salt appetite and thirst by glucocorticoids has been postulated to arise from glucocorticoid actions within the brain, affecting either mineralocorticoid (17, 35) or ANG II (3,6,8,22) receptors. For example, high levels of glucocorticoids are proposed to increase type I mineralocorticoid receptors and thus mineralocorticoid binding in the brain (17,35). Additionally, glucocorticoids may increase the number of ANG II receptors in the brain (22) and thereby augment the central actions of ANG II (which, in turn, may interact with mineralocorticoid receptors).Glucocorticoids also have systemic effects that could facilitate ingest...

Glucocorticoids Improve Renal Responsiveness to Atrial Natriuretic Peptide by Up-Regulating Natriuretic Peptide Receptor-A Expression in the Renal Inner Medullary Collecting Duct in Decompensated Heart Failure

“…The data presented here coupled with our previous findings suggest glucocorticoids could potentiate ANP's action in body fluid control by up-regulating NPR-A expression in the hypothalamus and kidney (Liu et al, 2010). The overall effect of glucocorticoids on body fluid is to have the body under systemic volume depletion (Thunhorst et al, 2007;Liu et al, 2010), which is consistent with the physiological effects of NPR-A activation on body fluid control. Our findings were also supported by data from humans.…”

“…However, emerging evidence overthrew this notion and demonstrated that the rise in blood pressure is very likely caused by the increased pressor responsiveness induced by glucocorticoids (Turner et al, 1996;Wallerath et al, 1999;Whitworth et al, 2000). Contrary to the notion that glucocorticoids cause renal water and sodium retention, evidence showed glucocorticoid administration could produce potent diuresis and natriuresis in rats (Thunhorst et al, 2007;Liu et al, 2010). It has also been found, in clinical observations, that chronic glucocorticoid administration could produce potent diuresis and restore body fluid homeostasis in patients with heart failure and severe fluid overload (Liu et al, 2006(Liu et al, , 2007Zhang et al, 2008;Massari et al, 2011).…”

Role of Mineralocorticoid Receptor on Experimental Cerebral Aneurysms in Rats

“…In previous studies, treatment with MR antagonists increased or did not affect urinary sodium excretion. 22,34,35 Thunhorst et al 36 showed that DOCA treatment progressively increased sodium ingestion, and the sodium intake exceeded the urinary sodium excretion; they suggested that the mechanisms underlying these effects involve actions on the brain that affect the central binding of Ang II and mineralocorticoid. Furthermore, Titze et al 37 showed that DOCA-salt led to a total-body sodium excess.…”

Possible Contribution of Mineralocorticoid Receptor Activation on Glucocorticoid-Induced Left Ventricular Remodeling in Adrenalectomized Rat

“…The mRNA levels of brain natriuretic peptide (BNP), atrial natriuretic peptide (ANP) and transforming growth factor-â 1 (TGF-â1) were measured as previously described 12 and MR, glucocorticoid receptor (GR), SGK1, 11âHSD2 were measured as previously described 1 . cDNA was initially denatured at 95 o C for 30 sec, and then amplified by PCR for 48 cycles (95 o C for 15 sec, 60 o C for 1 min) 13,14 . The oligonucleotide primer sequences for the rat CYP11B2 (NM_012538) are sense: 5'-AAAGAAGGTGCG TCAGAATGC-3', antisense: 5'-ACTTCAGG CTACCAGGGTTCAG-3'.…”