Role of angiotensin II in dietary modulation of rat late distal tubule bicarbonate flux in vivo.

Levine, David Z.; Iacovitti, Michelle; Buckman, S.; Burns, Kevin D.

doi:10.1172/jci118378

Cited by 69 publications

(30 citation statements)

References 21 publications

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“…13 The view that ␣ENaC abundance is regulated via AT 1 receptor occupation has derived additional support from a previous study in which ablation of the AT 1a receptor gene in mice resulted in a marked decrease in ␣ENaC protein abundance despite an increase in circulating aldosterone levels. 28 These data add to evidence from micropuncture studies 6,31,32 and patch clamp studies of isolated collecting ducts 33 that angiotensin II has the direct effect of regulating ion transport in the connecting tubule and collecting duct. Additionally, immunohistochemical studies 34 and RT-PCR studies 35 have provided evidence for expression of AT 1 receptors in collecting duct.…”

Section: Discussionmentioning

confidence: 77%

Long-Term Regulation of ENaC Expression in Kidney by Angiotensin II

et al. 2003

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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...

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Section: Discussionmentioning

confidence: 77%

Long-Term Regulation of ENaC Expression in Kidney by Angiotensin II

et al. 2003

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“…The presence of angiotensin II type 1 (AT 1 ) receptors in the luminal and basolateral membranes of DCT epithelia offers a potential role for ANG II to directly regulate the DCT sodium transport (10, 25). ANG II has been shown to stimulate transport of bicarbonate, fluid, and sodium in the DCT (34), and proliferation of the DCT in an ANG II-mediated renal injury model (19,20). Additionally, chronic treatment with the AT 1 receptor antagonist candesartan together with vasopressin decreased NCC abundance compared with control or treatment with vasopressin alone (15).…”

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confidence: 99%

ANG II provokes acute trafficking of distal tubule Na⁺-Cl⁻cotransporter to apical membrane

Sandberg¹,

Riquier²,

Pihakaski-Maunsbach³

et al. 2007

American Journal of Physiology-Renal Physiology

142

149

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May 16, 2007; doi:10.1152/ajprenal.00064.2007.-The distal convoluted tubule (DCT) Na ϩ -Cl Ϫ cotransporter (NCC), the target of thiazide diuretics, is responsible for the reabsorption of 5-10% of filtered NaCl. The aim of this study was to test the hypothesis that acute infusion of the angiotensin-converting enzyme (ACE) inhibitor captopril (at 12 g/min) for 20 min provokes trafficking of NCC from apical plasma membranes (APM) to subapical cytoplasmic vesicles (SCV), which is reversed by acute ANG II infusion (ANG II at 20 ng ⅐ kg Ϫ1 ⅐ min Ϫ1 along with 12 g/min captopril) for 20 min in male Sprague-Dawley rats (250 -350 g). By immuno-electron microscopy using an anti-NCC (D. Ellison) 71.5 Ϯ SD 4.9% of the NCC gold labeling was associated with the APM in control, sham operated, and infused rats, while captopril infusion reduced NCC in APM to 54.9 Ϯ 6.9% (P Ͻ 0.001) and markedly increased immunogold labeling of SCV. Subsequent infusion of ANG II with captopril restored NCC immunogold labeling of APM to 72.4 Ϯ 4.2%, that is, 20% of the total NCC trafficked between APM and SCV. Likewise, on density gradients of cortex, captopril provoked redistribution of 27.3% of total NCC from low-density APM-enriched membranes to higher-density membranes and ANG IIϩcaptopril restored 20.3% of the NCC to APM-enriched fractions. Redistribution occurred independent of a change in NCC total abundance. In conclusion, this study demonstrates that ACE inhibition provokes acute trafficking of NCC out of the plasma membrane, which likely decreases DCT Na ϩ reabsorption, while ANG II provokes rapid trafficking of NCC from stores in subapical vesicles to the plasma membrane, which likely increases DCT Na ϩ reabsorption. sodium transport; thiazide receptor; immunoelectron microscopy THE NA ϩ -CL Ϫ COTRANSPORTER (NCC) is expressed in the apical membrane of the distal convoluted tubule (DCT) and is the target of the thiazide diuretics, which are frequently used in the treatment of hypertension and edema (1, 29). The importance of NCC in the regulation of blood pressure and salt balance is demonstrated in the genetic disorder Gitelman's syndrome in which loss of function mutations in NCC results in salt wasting, hypokalemia, and hypotension (32). Studies in mice with NCC knocked out show that on low-sodium diets, blood pressure is significantly reduced from control (31).There are multiple mechanisms by which NCC could be regulated to control Na ϩ transport in the DCT. Many studies have shown that NCC abundance is regulated by stimuli, such as dietary salt, aldosterone escape, and mineralocorticoid receptor blockade (22,26,33,36), less is known about trafficking of NCC to and from the apical membrane as a way of regulating NCC. The potential importance of trafficking in the regulation of NCC has been demonstrated in vitro in Gitelman's syndrome where oocyte studies indicate that NCC is not processed properly in the endoplasmic reticulum, resulting in deficient trafficking of NCC to the plasma membrane (8,14). A previous study from this labora...

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confidence: 99%

“…Studies have reported that AngII can alter transport in distal tubular segments (7,8), cortical collecting ducts (9), and macula densa cells (10,11). In the distal tubule and cortical collecting duct, AngII may stimulate Na:H exchange (7)(8)(9). Also of potential importance is the findings by Wang and Giebisch (12) that the effects of AngII to stimulate volume reabsorption in the late distal tubule not only involves the acid base transporters (Na:H exchange and NaHCO 3 cotransport) but may act via Na ϩ channels.…”

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confidence: 99%

Angiotensin II Directly Stimulates ENaC Activity in the Cortical Collecting Duct via AT1 Receptors

Peti‐Peterdi

Warnock

Bell

2002

Journal of the American Society of Nephrology

279

243

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Abstract. Angiotensin II (AngII) helps to regulate overall renal tubular reabsorption of salt and water, yet its effects in the distal nephron have not been well studied. The purpose of these studies was to determine whether AngII stimulates luminal Na ϩ transport in the cortical collecting duct (CCD). Intracellular Na ϩ concentration ([Na ϩ ] i ), as a reflection of Na ϩ transport across the apical membrane, was measured with fluorescence microscopy using sodium-binding benzofuran isophthalate (SBFI) in isolated, perfused CCD segments dissected from rabbit kidneys. Control [Na ϩ ] i , during perfusion with 25 mM NaCl and a Na ϩ -free solution in the bath containing the Na ϩ -ionophore monensin (10 M, to eliminate basolateral membrane Na ϩ transport) averaged 19.3 Ϯ 5.2 mM (n ϭ 16). Increasing luminal [NaCl] to 150 mM elevated [Na ϩ ] i by 9.87 Ϯ 1.5 mM (n ϭ 7; P Ͻ 0.05). AngII (10 Ϫ9 M) added to the lumen significantly elevated baseline [Na ϩ ] i by 6.3 Ϯ 1.0 mM and increased the magnitude (⌬ ϭ 25.2 Ϯ 3.7 mM) and initial rate (Ϸ5 fold) of change in [Na ϩ ] i to increased luminal [NaCl]. AngII when added to the bath had similar stimulatory effects; however, AngII was much more effective from the lumen. Thus, AngII significantly increased the apical entry of Na ϩ in the CCD. To determine if this apical entry step occurred via the epithelial Na ϩ channel (ENaC), studies were performed using the specific ENaC blocker, benzamil hydrochloride (10 Ϫ6 M). When added to the perfusate, benzamil almost completely inhibited the elevations in [Na ϩ ] i to increased luminal [NaCl] in both the presence and absence of AngII. These results suggest that AngII directly stimulates Na ϩ channel activity in the CCD. AT 1 receptor blockade with candesartan or losartan (10 Ϫ6

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Role of angiotensin II in dietary modulation of rat late distal tubule bicarbonate flux in vivo.

Cited by 69 publications

References 21 publications

Long-Term Regulation of ENaC Expression in Kidney by Angiotensin II

Long-Term Regulation of ENaC Expression in Kidney by Angiotensin II

ANG II provokes acute trafficking of distal tubule Na⁺-Cl⁻cotransporter to apical membrane

Angiotensin II Directly Stimulates ENaC Activity in the Cortical Collecting Duct via AT1 Receptors

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Role of angiotensin II in dietary modulation of rat late distal tubule bicarbonate flux in vivo.

Cited by 69 publications

References 21 publications

Long-Term Regulation of ENaC Expression in Kidney by Angiotensin II

Long-Term Regulation of ENaC Expression in Kidney by Angiotensin II

ANG II provokes acute trafficking of distal tubule Na+-Cl−cotransporter to apical membrane

Angiotensin II Directly Stimulates ENaC Activity in the Cortical Collecting Duct via AT1 Receptors

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ANG II provokes acute trafficking of distal tubule Na⁺-Cl⁻cotransporter to apical membrane