Interaction of exogenous ouabain and chronic mineralocorticoid treatment in the kidney of the conscious sheep.

1. Ouabain is known to have natriuretic effects only at high doses, and therefore if endogenously produced ouabain has a role in the regulation of sodium excretion, the renal response to ouabain must be increased substantially in certain physiological situations. The aim of this study is to determine whether treatment with the mineralocorticoid, aldosterone, potentiates that natriuretic response to ouabain. 2. Six conscious sheep received renal arterial infusion of either vehicle or aldosterone (3 micrograms/h). Forty hours after commencement of infusion ouabain was infused into the renal artery at 400 micrograms/h for 60 min. A second infusion of ouabain was administered on the 6th day of aldosterone treatment. 3. In the absence of aldosterone, the effects on sodium excretion produced by ouabain infusion at 400 micrograms/h into the renal artery were variable and not statistically significant. Ouabain infusion after 40 h of aldosterone treatment increased sodium excretion from 40 +/- 14 to 676 +/- 69 mumol/min in the second hour following cessation of ouabain infusion (P < 0.001). Ouabain infusion after 6 days of aldosterone treatment increased sodium excretion similarly. Ouabain-stimulated sodium excretion was significantly greater during aldosterone treatment compared to vehicle treatment (P < 0.05). In contrast, no enhancement of effect was observed after acute treatment with aldosterone. 4. These results demonstrate potentiation of the natriuretic response to ouabain infusion by chronic mineralocorticoid treatment and suggest a potential role of endogenous digitalis-like factor in the physiological control of sodium homeostasis.