Differential acute effects of aldosterone, dexamethasone, and hyperkalemia on distal tubular potassium secretion in the rat kidney.

Field, Michael J.; Stanton, Bruce A.; Giebisch, Gerhard

doi:10.1172/jci111598

Cited by 131 publications

(86 citation statements)

References 41 publications

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“…Young and Paulsen stressed the powerful effect of increased plasma K + levels on renal K + excretion.25 years ago. 39 However, although elevation of plasma K + concentrations by intravenous K + infusions increases apical K + conductances in distal tubules, 23,57 reduces NCC phosphorylation, and drives kaliuresis, 58 ex vivo studies on mouse CD cells and isolated renal tubules failed to detect any significant direct effects of increased extracellular K + concentrations on ENaC and ROMK channel activities 59 and NCC phosphorylation. 35 In summary, AS 2/2 mice adapt to physiologically relevant challenges in dietary K + intake without major signs of illnesses and hyperkalemia.…”

Section: Discussionmentioning

confidence: 99%

Mechanisms of Renal Control of Potassium Homeostasis in Complete Aldosterone Deficiency

Todkar

Picard²,

Loffing‐Cueni³

et al. 2015

Journal of the American Society of Nephrology

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Aldosterone-independent mechanisms may contribute to K + homeostasis. We studied aldosterone synthase knockout (AS 2/2 ) mice to define renal control mechanisms of K + homeostasis in complete aldosterone deficiency. AS 2/2 mice were normokalemic and tolerated a physiologic dietary K + load (2% K + , 2 days) without signs of illness, except some degree of polyuria. With supraphysiologic K + intake (5% K + ), AS 2/2 mice decompensated and became hyperkalemic. High-K + diets induced upregulation of the renal outer medullary K + channel in AS 2/2 mice, whereas upregulation of the epithelial sodium channel (ENaC) sufficient to increase the electrochemical driving force for K + excretion was detected only with a 2% K + diet. Phosphorylation of the thiazide-sensitive NaCl cotransporter was consistently lower in AS 2/2 mice than in AS +/+ mice and was downregulated in mice of both genotypes in response to increased K + intake.Inhibition of the angiotensin II type 1 receptor reduced renal creatinine clearance and apical ENaC localization, and caused severe hyperkalemia in AS 2/2 mice. In contrast with the kidney, the distal colon of AS 2/2 mice did not respond to dietary K + loading, as indicated by Ussing-type chamber experiments. Thus, renal adaptation to a physiologic, but not supraphysiologic, K + load can be achieved in aldosterone deficiency by aldosteroneindependent activation of the renal outer medullary K + channel and ENaC, to which angiotensin II may contribute. Enhanced urinary flow and reduced activity of the thiazide-sensitive NaCl cotransporter may support renal adaptation by activation of flow-dependent K + secretion and increased intratubular availability of Na + that can be reabsorbed in exchange for K + secreted.

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Section: Discussionmentioning

confidence: 99%

Mechanisms of Renal Control of Potassium Homeostasis in Complete Aldosterone Deficiency

Todkar

Picard²,

Loffing‐Cueni³

et al. 2015

Journal of the American Society of Nephrology

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“…Thereafter, the rabbits were maintained on glucocorticoid replacement therapy (dexamethasone 10 pg/kg s.c.) from the second postoperative day until death ( 12-15 d). This dose ofglucocorticoid minimizes mineralocorticoid activity, while enhancing food and water intake as well as the general well-being of the animals (18)(19)(20).…”

Section: Methodsmentioning

confidence: 99%

Mineralocorticoid modulation of apical and basolateral membrane H+/OH-/HCO3- transport processes in the rabbit inner stripe of outer medullary collecting duct.

Hays

1992

J. Clin. Invest.

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To examine the mechanism by which mineralocorticoids regulate HCO3-absorption in the rabbit inner stripe of the outer medullary collecting duct, we microfluorometrically measured intracellular pH (pH1) in in vitro perfused tubules using 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein (BCECF) assaying the apical and basolateral membrane H'/OH-/HCO3 (control, 72.7±15.7 pmol -mm-' * min-vs DOCA, 132.3±22.5 pmol. mm-1 min-', P < 0.02), while the K112 for Cl-was unchanged. Basolateral membrane Na+/H+ antiporter activity assayed as the Na+-dependent pH1 recovery from an acid load was not changed in chronic DOCA tubules versus controls. In conclusion, the apical membrane H+ pump and basolateral membrane Cl-/HCO3 exchanger of the rabbit OMCDI are regulated in parallel without chronic alterations in pH1 under the conditions of mineralocorticoid excess and deficiency. The parallel changes in these transporters accounts for the alterations in OMCDj HCO3 absorption seen under these condi-

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“…K secretion is regulated by hormones such as vasopressin (1,2,8) and aldosterone and dietary K intake (11,12,26,34). A large body of evidence has demonstrated that a low-K intake decreases, whereas a high-K intake increases renal K secretion (3,4,13,24).…”

mentioning

confidence: 99%

Effect of hydrogen peroxide on ROMK channels in the cortical collecting duct

Wei¹,

Wang²,

Babilonia³

et al. 2007

American Journal of Physiology-Renal Physiology

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We used the patch-clamp technique to study the effect of H2O2 on the apical ROMK-like small-conductance K (SK) channel in the cortical collecting duct (CCD). The addition of H2O2 decreased the activity of the SK channels and the inhibitory effect of H2O2 was larger in the CCD from rats on a K-deficient diet than that from rats on a normal-K or a high-K diet. However, application of H2O2 did not inhibit the SK channels in inside-out patches. This suggests that the H2O2-mediated inhibition of SK channels was not due to direct oxidation of the SK channel protein.Because a previous study showed that H2O2 stimulated the expression of Src family protein tyrosine kinase (PTK) which inhibited SK channels (3), we explored the role of PTK in mediating the effect of H2O2 on SK channels. The application of H2O2 stimulated the activity of endogenous PTK in M-1 cells and increased tyrosine phosphorylation of ROMK in HEK293 cells transfected with GFP-ROMK1 and c-Src. However, blockade of PTK only attenuated but did not completely abolish the inhibitory effect of H2O2 on SK channels. Since H2O2 has also been demonstrated to activate mitogen-activated protein kinase, P38, and ERK (3), we examined the role of P38 and ERK in mediating the effect of H2O2 on SK channels. Similar to blockade of PTK, suppression of P38 and ERK did not completely abolish the H2O2-induced inhibition of SK channels. However, combined use of ERK, P38, and PTK inhibitors completely abolished the effect of H2O2 on SK channels. Also, treatment of the CCDs with concanavalin A, an agent which has been shown to inhibit endocytosis (19), abolished the inhibitory effect of H2O2. We conclude that addition of H2O2 inhibited SK channels by stimulating PTK activity, P38, and ERK in the CCD and that H2O2 enhances the internalization of the SK channels.

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Differential acute effects of aldosterone, dexamethasone, and hyperkalemia on distal tubular potassium secretion in the rat kidney.

Cited by 131 publications

References 41 publications

Mechanisms of Renal Control of Potassium Homeostasis in Complete Aldosterone Deficiency

Mechanisms of Renal Control of Potassium Homeostasis in Complete Aldosterone Deficiency

Mineralocorticoid modulation of apical and basolateral membrane H+/OH-/HCO3- transport processes in the rabbit inner stripe of outer medullary collecting duct.

Effect of hydrogen peroxide on ROMK channels in the cortical collecting duct

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