Mineralocorticoid modulation of rabbit medullary collecting duct acidification. A sodium-independent effect.

Abstract

A B S T R A C T Rabbit medullary collecting duct (MCD) from inner stripe of outer medulla has been identified as a major distal nephron acidification site. The isolated, perfused tubule technique was used to examine the roles of mineralocorticoid and glucocorticoid in regulation of MCD acidification. Surgical adrenalectomy reduced bicarbonate reabsorptive rate (JHCO3, pmol * mm-'l min-') from the normal of 9.79±1.21 to 0.67±1.1. Chronic administration of deoxycorticosterone acetate (DOCA) increased JHCO3 of MCD significantly to 18.02±1.62 whereas chronic dexamethasone administration did not affect JHCO3. The direct effects of aldosterone and dexamethasone upon MCD acidification were examined by perfusing tubules harvested from adrenalectomized rabbits in the presence of aldosterone or dexamethasone. Aldosterone, at 5 X 10-8 M, increased JHCO3 significantly from 1.27±0.28 to 3.09±0.34. At 10-6 M, aldosterone produced a greater increase in JHCO3 from 0.67±1.1 to 9.39±1.59. In vitro dexamethasone treatment had no effect on JHCO3. Studies examining the sodium dependence of aldosterone-stimulated acidification demonstrated that JHCO3 in tubules harvested from normal and deoxycorticosterone acetate-treated animals was unaffected by total replacement of sodium with tetramethylammonium. Likewise, luminal amiloride (5 X 10-5 M) had no effect on JHCO3 in tubules har-

Acid-Base Homeostasis

“…Interestingly, the cell voltages of ICs are strikingly different from most cells, including principal cells: first, although there is little data, the cell-negative voltages as shown in Figure 4 are much less (less negative), and second, the cells are energized by the H 1 pump rather than by Na-K-ATPase as in most cells (54,57,58). H 1 secretion, including in the medullary collecting tubule, is also directly stimulated by mineralocorticoids, not just by secondary electrical effects (59,60). Distal tubule acidification may be strongly influenced by chloride concentration gradients between tubular lumen and peritubular blood; this may result both from voltage changes and by direct lumen to cell concentration gradients driving pendrin and other transporters.…”

Mechanisms in Hyperkalemic Renal Tubular Acidosis

“…In addition, aldosterone has a direct, Naindependent, nongenomic effect on proton secretion through upregulation of apical proton pumps on intercalated cells, in rodents at least. 2,3 TRUE HYPOALDOSTERONISM Low levels of aldosterone or tubular unresponsiveness to this hormone are present in the majority of patients with hyperkalemia and impaired renal function before end stage. 4,5 The most common medical conditions associated with hyporeninemic hypoaldosteronism include diabetes and various forms of interstitial disease, including amyloid, monoclonal gammopathies, and particularly the interstitial nephritis associated with nonsteroidal anti-inflammatory agents.…”

Nongenomic stimulation of vacuolar H + -ATPases in intercalated renal tubule cells by aldosterone

“…In the connecting segment and cortical collecting duct, aldosterone stimulates the electrogenic vacuolar H ϩ -ATPase through increased reabsorption of Na ϩ in principal cells, which renders the tubule lumen more negative and thus facilitates proton diffusion into the lumen (1). In the outer medullary collecting duct, aldosterone also stimulates proton secretion, but this effect persists in the absence of Na ϩ absorption, suggesting direct activation of vacuolar H ϩ -ATPase activity (8). Long-term stimulation of acidification by aldosterone has been described in rabbit and rat outer medullary collecting ducts (9)(10)(11).…”