Effect of mineralocorticoids on spontaneous sodium chloride appetite of adrenalectomized rats

Evaluation of RU28318 and RU40555 as selective mineralocorticoid receptor and glucocorticoid receptor antagonists, respectively: receptor measures and functional studies

“…We used aldosterone regulation of sodium intake as a bioassay to study the in vivo effectiveness of RU28318 as a MR antagonist. As previously reported [28,29], we found that rats signi®cantly increased their preference for saline containing water over tap water after adrenalectomy, and that this effect was reversed by aldosterone treatment. RU28318 treatment was able to block the normalizing effect of aldosterone on saline intake.…”

“…This test relies on the voluntary increased saline intake observed in rats after adrenalectomy. Low dose aldosterone replacement is known to reverse the increased saline intake [28,29]. Subjects were individually housed and were given the choice of two drinking bottles ®lled with either tap water or 0.9% saline.…”

“…One of the best characterized physiological roles of MR is mediation of sodium retention by the kidney and a complementary regulation of sodium appetite [27]. Adrenalectomy of rats results in increased sodium intake, which can be normalized by treatment with the MR selective agonist, aldosterone [28,29]. Therefore, we have tested the ability of RU28318 to functionally antagonize this MR mediated effect by examining saline intake in adrenalectomized rats treated with aldosterone 2RU28318.…”

Aldosterone Target Neurons in the Nucleus Tractus Solitarius Drive Sodium Appetite

“…Aldosterone is not required for sodium appetite (Richter, 1936), but it enhances salt intake. Although a small dose in adrenalectomized (adx) rats reduces the sodium losses that otherwise would induce sodium appetite (Fregly and Waters, 1966), higher doses of aldosterone and other adrenal mineralocorticoids increase sodium intake even in the absence of sodium deficiency (Rice and Richter, 1943;Wolf, 1965;Wolf and Handal, 1966). In fact, deoxycorticosterone acetate (DOCA) stimulates a pattern of saline ingestion nearly indistinguishable from adrenalectomy (Stricker et al, 1992).…”

General

“…Inhibition studies suggest that a single carrier transports both these peptides. (Avrith & Fitzsimons, 1980) and mineralocorticoids (Fregly & Waters, 1966), given separately or in combination. We have found that sodium appetite can be stimulated in rats by causing apparent mineralocorticoid excess using glycyrrhizic acid (GZA) to block l lfl-hydroxysteroid dehydrogenase (1 1l-OHSD) which normally protects the mineralocorticoid receptor from stimulation by the relatively (to aldosterone) large amounts of glucocorticoid (Edwards, 1991).…”