Rapid natriuretic action of aldosterone in the rat

Abstract

Rapid, nongenomic actions of aldosterone have been demonstrated in a number of cell types in vitro, including renal cell lines, but there remains little direct evidence that it is able to exert rapid effects on the kidney in the whole animal. Accordingly, the aim of this study was to determine whether aldosterone induces rapid changes in the renal handling of electrolytes or acid-base balance in the anesthetized rat. With the use of a servo-controlled fluid replacement system, spontaneous urine output by anesthetized male Sprague-Dawley rats was replaced with 2.5% dextrose. After a 3-h equilibration and a 1-h control period, rats were infused with aldosterone (42 pmol/min) or vehicle for 1 h. Aldosterone infusion induced a rapid (within 15 min) increase in sodium excretion that peaked at 0.24 +/- 0.08 compared with 0.04 +/- 0.01 micromol x min(-1) 100 x body weight(-1) (P = 0.041) in the vehicle-infused rats. This natriuresis was not associated with changes in glomerular filtration rate; urine flow rate; potassium, chloride, or bicarbonate excretion; or urine pH. The mechanisms involved are unclear, but because we have previously shown that aldosterone stimulates a rapid (4 min) increase in cAMP generation in the rat inner medullary collecting duct (IMCD) (Sheader EA, Wargent ET, Ashton N, and Balment RJ. J Endocrinol 175: 343-347, 2002), they could involve cAMP-mediated activation of the cystic fibrosis transmembrane conductance regulator chloride channel, which drives sodium secretion in the IMCD.

Mechanisms Underlying Rapid Aldosterone Effects in the Kidney

“…Here ERK1/2 is also activated but in turn suppresses basolateral NHE1 activity, which indirectly inhibits apical NHE3. Aldosterone infusion promotes a transient rise in Na + excretion from the kidneys of experimental animals within 15 min of commencement; this transient rise subsides when infusion is stopped (112). This early phase of increased Na + excretion was not mirrored by a change in HCO 3 − , K + , or Cl − excretion or a change in urinary pH.…”

Nongenomic Actions of Aldosterone on the Renal Tubule

“…In contrast, in recent studies of adrenal-intact, anesthetized rats, intravenous infusion of aldosterone induced an increase in Na ϩ excretion within 15 minutes, with no detectable change in Cl Ϫ , K ϩ , or HCO 3 Ϫ excretion or urine pH. 61 The significance of this effect remains to be determined, because it is opposite to aldosterone's antinatriuretic function. It is unclear whether the differing effects on Na ϩ and K ϩ excretion in the 2 studies are the result of the difference in species, the hormonal or electrolyte status of the animals before aldosterone administration, or other factors.…”

“…35 Consistent with this view, rapid infusion of aldosterone into intact rats induced a significant change in renal Na ϩ excretion with no effect on urinary pH or acid excretion. 61 On the other hand, the nongenomic inhibition of HCO 3 Ϫ absorption in the MTAL may contribute to acid-base disorders associated with changes in systemic potassium balance. For example, an increase in NHE3 activity and HCO 3 Ϫ absorption in the MTAL in response to a reduced plasma aldosterone level could contribute to the increased renal HCO 3 Ϫ absorptive capacity that promotes metabolic alkalosis in K ϩ depletion.…”

Mechanisms of Mineralocorticoid Action

“…Although these effects have been demonstrated in a range of tissues, evidence supporting a physiological relevance for these rapid effects is limited. 60,61 Studies have predominantly been in vitro; however, recently, rapid reductions in forearm blood flow in conscious subjects after aldosterone infusions have been reported in some but not all studies. 49,60 These studies do not distinguish the cell types involved but demonstrate that physiologically measurable effects are possible in the same time frame.…”