Abstract-Aldosterone and other mineralocorticoids increase citrate synthase activity in the kidney and enhance renal sodium reabsorption, but it is unclear whether the increased citrate synthase activity is involved in renal sodium transport. We used the Wistar-Furth rat, an inbred strain found to be deficient in renal citrate synthase activity, as an experimental model to investigate this issue. We confirmed that renal citrate synthase activity from adrenalectomized Wistar-Furth rats was decreased compared with that from control Wistar rats (by 28% T he mineralocorticoid aldosterone stimulates activity of certain key enzymes in the tricarboxylic acid cycle (eg, citrate synthase) in the rat kidney. 1-5 Adrenalectomy reduces renal citrate synthase activity, and the administration of aldosterone to adrenalectomized animals restores citrate synthase activity. 4 These findings arose from an ongoing effort to identify aldosterone-induced proteins (ie, proteins synthesized in response to the transcription factor activity of the occupied mineralocorticoid receptor) and to determine how these proteins mediate the classic action of mineralocorticoids: renal sodium reabsorption. It has been hypothesized that enhancement of citrate synthase activity increases ATP formation and, subsequently, activity of Na ϩ ,K ϩ -ATPase and sodium reabsorption in the distal nephron. This schema is consistent with the "energy hypothesis" of aldosterone action.However, the correlation of aldosterone-induced enhancement of renal citrate synthase activity with aldosteroneinduced stimulation of sodium reabsorption has been investigated in only a few studies, and the results have been inconsistent. At 3 to 4 hours after aldosterone was injected into rats, both a maximum increase in renal citrate synthase activity and a maximum decrease in urinary sodium-topotassium ratio were observed. 3 Other studies have been performed in cultured cell lines. In toad bladder and toad kidney cells, aldosterone stimulated sodium transport without an increase in citrate synthase activity. 6 In another study, aldosterone stimulated both vectorial sodium transport and citrate synthase activity in toad bladder cells, whereas aldosterone stimulated sodium transport in the absence of an increase in citrate synthase activity in A6 cells. 7 In the present study, we used Wistar-Furth rats (WF) as an experimental model to investigate the role of citrate synthase activity in aldosterone-mediated sodium reabsorption. WF, which were bred from normal Wistar rats (W), have been shown to be resistant to the development of mineralocorticoid-excess hypertension. 8 -13 During the biochemical evaluation of the mechanisms that underlie this resistance to mineralocorticoids, we observed that basal and aldosterone-stimulated citrate synthase activities in whole kidney were markedly reduced in WF compared with W. 13