Abstract-We carried out semiquantitative immunoblotting of kidney to identify apical sodium transporter proteins whose abundances are regulated by angiotensin II. In NaCl-restricted rats (0.5 mEq Na/200 g BW/d), the type 1 angiotensin II receptor (AT 1 receptor) antagonist, candesartan, (1 mg/kg of body weight per day SC for 2 days) markedly decreased the abundance of the ␣ subunit of the epithelial sodium channel (ENaC). This subunit has been shown to be rate-limiting for assembly of mature ENaC complexes. In addition, systemic infusion of angiotensin II increased ␣ENaC protein abundance in rat kidney cortex. The decrease in ␣ENaC protein abundance in response to AT 1 receptor blockade was associated with a fall in ␣ENaC mRNA abundance (real-time RT-PCR), consistent with transcriptionally mediated regulation. The effect of AT 1 receptor blockade on ␣ENaC expression was not blocked by spironolactone, suggesting a direct role of the AT 1 receptor in regulation of ␣ENaC gene expression. Candesartan administration was also found to increase the abundances of the ␤ and ␥ subunits. The increase in ␤ and ␥ENaC protein abundance was not associated with a significant increase in the renal abundances of the corresponding mRNAs, suggesting a posttranscriptional mechanism. Immunocytochemistry confirmed the increase in ␤ and ␥ENaC protein abundance and demonstrated candesartan-induced ENaC internalization in collecting duct cells. The results support the view that the angiotensin II receptor regulates ENaC abundance, consistent with a role for angiotensin II in regulation of collecting duct function. Key Words: receptors, angiotensin II Ⅲ angiotensin antagonist Ⅲ sodium channels Ⅲ aldosterone L ong-term control of blood pressure is closely tied to sodium balance and extracellular fluid volume regulation, both of which are controlled in part by the renin-angiotensin-aldosterone system (RAAS). 1 Angiotensin II has important nonrenal effects that are instrumental in the control of blood pressure as both a vasoconstrictor and a regulator of aldosterone secretion. In addition, angiotensin II has direct effects on the renal tubule in regulating NaCl reabsorption. 2 The direct antinatriuretic effects of angiotensin II appear to be particularly important in conditions of dietary sodium restriction or contraction of extracellular fluid volume. 1 Regulation of renal tubule sodium transport by angiotensin II has been investigated chiefly in relatively short-term experiments with observations within a few minutes of angiotensin II addition. 3-7 However, there is growing evidence that a variety of mediators of transport regulation in the kidney, such as vasopressin 8 and aldosterone, 9 work by both short-term and long-term actions. The long-term actions are associated with adaptive increases in abundance of transporter proteins, whereas short-term actions are generally associated with regulated trafficking or posttranslational modifications of the transporter proteins.The antinatriuretic effects of angiotensin II on sodium transport are...

Background/Aims: Abnormal serum potassium is associated with higher mortality in dialysis patients, but its impact on outcomes in predialysis chronic kidney disease (CKD) is less clear. Furthermore, blacks with normal kidney function have lower urinary potassium excretion, but it is unclear if such differences have a bearing on race-associated outcomes in CKD. Methods: We studied predialysis mortality and slopes of estimated glomerular filtration rate, eGFR) associated with serum potassium in 1,227 males with CKD. Mortality was examined in time-dependent Cox models, and slopes of eGFR in linear mixed effects models with adjustments for case mix and laboratory values. Results: Both hypo- and hyperkalemia were associated with mortality overall and in 933 white patients, but in 294 blacks hypokalemia was a stronger death predictor. Hypokalemia was associated with loss of kidney function independent of race: a 1 mEq/l lower potassium was associated with an adjusted difference in slopes of eGFR of -0.13 ml/min/1.73 m²/year (95% CI: -0.20 to -0.07), p < 0.001. Conclusion: Hypo- and hyperkalemia are associated with higher mortality in CKD patients. Blacks appear to better tolerate higher potassium than whites. Hypokalemia is associated with faster CKD progression independent of race. Hyperkalemia management may warrant race-specific consideration, and hypokalemia correction may slow CKD progression. This is a work of the US Government and is not subject to copyright protection in the USA. Foreign copyrights may apply. Published by S. Karger AG, Basel

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