In vivo effect of aldosterone on the cardiac Na+-K+ pump

In vitro exposure of cultured cardiac and non-cardiac cells to aldosterone (aldo) in high concentrations has been reported to upregulate the Na⁺-K⁺ pump. We examined the effect of in vivo aldosterone on the Na⁺-K⁺ pump. Rabbits received aldo for 7 days via osmotic minipumps to induce a modest increase in plasma aldosterone levels. Na⁺-K⁺ pump current (I_p) was measured in isolated ventricular myocytes. Mean I_p of myocytes from aldotreated rabbits was significantly (P<0.001) lower than mean I_p of myocytes from vehicle-control rabbits when the Na⁺ concentration in pipette solutions was near-physiological intracellular levels (10 mM). In contrast, aldo treatment did not alter pump activity when near-saturating levels of Na⁺ (80 mM) were used. To examine if the aldosterone-induced decrease in I_p was mediated by the classical mineralocorticoid receptor rabbits were treated with both aldo and spironolactone. Spironolactone treatment completely eliminated the aldosterone-induced pump inhibition. We conclude that the effect of modest elevations of aldosterone levels in vivo on the cardiac sarcolemmal Na⁺-K⁺ pump is the opposite of reported in vitro effects.