Independent effects of aldosterone and potassium on induction of potassium adaptation in rat kidney.

Abstract

We examined the independent effects of a high potassium diet and increased aldosterone levels on the development of renal potassium adaptation. This condition is defined by the increased ability of the kidneys to excrete an acute infusion of potassium. Rats were adrenalectomized (ADX) and received aldosterone at basal levels (0.5 Asg/100 g * d) or at high levels (2.0 ;g/100 go d) for 10 d. In each experimental group, animals received either a control diet or a high potassium diet. In ADX animals with basal aldosterone levels, a high potassium intake increased but did not completely restore the ability to excrete potassium and induced proliferation of the basolateral membrane of principal cells in the collecting tubule (i.e, morphologic adaptation). In contrast, increased aldosterone did not induce functional adaptation. Elevated aldosterone and dietary potassium intake were required to produce functional potassium adaptation indistinguishable from that in potassium-loaded, adrenal-intact animals.

Mechanisms of Renal Control of Potassium Homeostasis in Complete Aldosterone Deficiency

“…Consistently, a recent meta-analysis revealed that patients with a combined inhibition of aldosterone and angiotensin II action develop much more frequent episodes of severe hyperkalemia than patients with inhibition of either MR or AT1-dependent signaling. 45 Consistent with previous studies on adrenalectomized rats, 3,21,46 aldosterone-independent mechanisms cannot fully compensate for the loss of aldosterone. On a 5% K + diet, AS 2/2 mice but not AS +/+ mice decompensated, became hyperkalemic, and showed food avoidance.…”

“…Our finding that the activation of renal secretory K + channels in response to K + intake does not require aldosterone is consistent with previous ion transport and electrophysiologic studies on isolated CDs from adrenalectomized animals. 19,21 Although previous studies did not show a reduced creatinine clearance in AS 2/2 mice at baseline, 33 we saw a slight, although not statistically different, trend for a lowered creatinine clearance in AS 2/2 mice on a 2% K + diet ( Figure 5). To what extent a possibly reduced GFR may have contributed to the decompensation of the AS 2/2 mice on the 5% K + diet is open.…”

“…Previous studies on adrenalectomized rats and rabbits indicated that a high-K + diet increases renal Na + and K + channel activities independent from aldosterone. 19,[21][22][23] However, because adrenalectomies in rodents are often incomplete and the existence of local aldosterone producing systems in kidney and other organs have been suggested, 25 these previous studies could not exclude that minute amounts of remaining aldosterone production could have contributed to the observed activation of Na + and K + channels in the ASDN. In AS 2/2 mice, any aldosterone production is prevented because 39 This is in line with transport and renal clearance studies on adrenalectomized laboratory animals, which suggested that aldosterone is not absolutely necessary, but plays at least a permissive role and is important to achieve maximal K + secretion.…”

“…18 Moreover, even in adrenalectomized animals, increased K + intake augments K + excretion in kidney and colon. 3,21 Likewise, dietary K + increases apical Na + and K + channel conductances in the CD not only of intact but also of adrenalectomized rats 19,21 and rabbits. 22,23 However, adrenalectomy is not always complete and residual plasma aldosterone levels may persist.…”

Active proton secretion and potassium absorption in the rabbit outer medullary collecting duct. Functional evidence for proton-potassium-activated adenosine triphosphatase.

“…This form of metabolic alkalosis is usually secondary to mineralocorticoid excess and requires K depletion to produce maximal alkalinization ofthe extracellular fluid (21)(22)(23). Chronic hyperaldosteronism or exogenous mineralocorticoid therapy results in a three-to fourfold increase in K secretion in the cortical CD and initial collecting tubule (24)(25)(26), although effects on urinary K excretion are relatively minor (24). If net K secretion in the cortical CD and initial collecting tubule exceeds K intake, profound K depletion would ensue unless there were a compensatory increase in K-absorptive flux in more terminal nephron segments.…”