In vivo modulation of rat distal tubule net HCO3 flux by VIP, isoproterenol, angiotensin II, and ADH

Levine, David Z.; Iacovitti, Michelle; Buckman, S.; Harrison, V. C.

doi:10.1152/ajprenal.1994.266.6.f878

Cited by 24 publications

(31 citation statements)

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“…These data suggest that additional mechanisms contribute to augmented distal nephron acidification in HiPro rats. HiPro increases renal angiotensin II activity (30), and angiotensin II increases distal nephron acidification in vivo (31). Consequently, increased angiotensin II activity might contribute to the increment in distal nephron acidification that is not mediated by endothelin.…”

Section: Discussionmentioning

confidence: 99%

Endothelin-Induced Increased Nitric Oxide Mediates Augmented Distal Nephron Acidification as a Result of Dietary Protein

Wesson¹,

Simoni²,

Prabhakar³

2006

Journal of the American Society of Nephrology

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Tested was the hypothesis that enhanced nitric oxide (NO) production that is stimulated by increased renal endothelin activity mediates decreased distal nephron HCO 3 secretion that is induced by dietary protein. Munich-Wistar rats that ate minimum electrolyte diets with 50% casein-provided protein (HiPro) compared with controls that ate 20% protein for 3 wk had higher urine excretion of endothelin-1 (80 ؎ 15.7 versus 29 ؎ 3.9 fmol/kg body wt per d; P < 0.02) and of the NO metabolites NO 2 /NO 3 (21.2 ؎ 1.9 versus 14.9 ؎ 0.8 mol/kg body wt per d; P < 0.03). Bosentan, an endothelin A/B receptor antagonist, reduced HiPro rats' urine excretion of net acid (5859 ؎ 654 versus 8017 ؎ 1103 mol/d; P < 0.03, paired t test) and NO 2 /NO 3 (18.1 ؎ 1.1 versus 22.9 ؎ 2.0 mole/kg body wt per d; P < 0.05, paired t test). N-nitro-L-arginine methyl ester (L-NAME), an NO synthase inhibitor, also decreased urine net acid excretion (6621 ؎ 717 versus 8449 ؎ 1086 mol/d; P < 0.05, paired t test) but was not additive to bosentan. L-NAME increased in situ late distal nephron HCO 3 delivery in HiPro rats (18.8 ؎ 1.7 versus 9.6 ؎ 1.4 pmol/mm per min; P < 0.001) that was mediated by increased distal nephron HCO 3 secretion (؊7.2 ؎ 0.7 versus ؊3.5 ؎ 0.4 pmol/mm per min; P < 0. (3), the mechanism by which endothelin reduces distal nephron HCO 3 secretion is not known. In addition to increasing renal production of endothelin, increased dietary protein increases urine excretion of nitric oxide (NO) metabolites (4). Furthermore, endothelin increases renal NO production (5), and NO increases acidification in the proximal (6) and distal (7) nephron. Consequently, we tested the hypothesis that increased renal endothelin production that is induced by increased dietary protein reduces distal nephron HCO 3 secretion through increased NO. Materials and Methods Animals and Diet ProtocolMale and female Munich-Wistar rats (Harlan Sprague-Dawley, Houston, TX; 200 to 228 g) ate standard rat chow (Prolab RMH 2500 with 23% protein, Purina, Indianapolis, IN) for 1 wk, then ate a custom minimum electrolyte diet with protein as purified high nitrogen casein (ICN Nutritional Biochemicals, Cleveland, OH) for 3 wk and drank distilled H 2 O ad libitum. Rats that were on the high-protein diet (HiPro) ate custom diet with 50% protein, and controls ate 20%. In preliminary studies, similarweight rats ate 24.6 Ϯ 0.9 and 27.1 Ϯ 1.2 g/d, respectively (n ϭ 4, P ϭ 0.15), so all rats received 24 g/d diet to ensure similar diet intake and complete ingestion of drug mixed with diet in rats that were given drugs. Some received bosentan (Actelion, Allschwil, Switzerland), a nonpeptide endothelin A/B receptor antagonist (8), mixed with study diet at 100 mg/kg body wt per d. This oral dose blocks action of pressor doses of intravenous big ET-1 for Ͼ24 h (8). Preliminary studies determined that the minimal chronic dose of the NO synthase (NOS) inhibitor N-nitro-l-arginine methyl ester (L-NAME) that reduced urine net acid excretion (NAE) in paired HiPro rats (6451 Ϯ 785 versus 848...

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Section: Discussionmentioning

confidence: 99%

Endothelin-Induced Increased Nitric Oxide Mediates Augmented Distal Nephron Acidification as a Result of Dietary Protein

Wesson¹,

Simoni²,

Prabhakar³

2006

Journal of the American Society of Nephrology

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“…Rats were anesthetized with 100 mg/kg Inactin (BYK Gulden, Konstanz, Germany) and prepared for micropuncture as described previously (2). Briefly, the animal was placed on a heated operating table and a tracheostomy was performed, using PE-240 tubing.…”

Section: Methodsmentioning

confidence: 99%

“…Perfusate and sample tCO 2 concentrations were measured by microcalorimetry as described previously (2). Micropuncture and sample handling pipettes contained Hepes-buffered mineral oil, and the samples were placed on a quartz dish flooded with Hepes-buffered mineral oil.…”

Section: Methodsmentioning

confidence: 99%

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

Levine¹,

Iacovitti²,

Buckman³

et al. 1996

J. Clin. Invest.

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We have reported that overnight fasting stimulates bicarbonate reabsorption (J tCO2 ) in rat distal tubules. The present in vivo microperfusion studies evaluated the hypothesis that endogenous angiotensin II (AII) mediates this response. Rat late distal (LD) tubules were perfused at 8 nl/min in vivo with a hypotonic solution containing 28 mM bicarbonate. In overnight-fasted rats, LD J tCO2 was significantly higher than in normally fed rats (50 Ϯ 4 vs. 16 Ϯ 6 pmol/min и mm, P Ͻ 0.05). When overnight-fasted rats were salt-loaded, J tCO2 fell significantly (38 Ϯ 3 pmol/min и mm, P Ͻ 0.05). Conversely, in fed rats ingesting a zero-salt diet, J tCO2 increased threefold (45 Ϯ 5 pmol/min и mm, P Ͻ 0.05). Enalaprilat infusion (0.25 g/kg body wt, intravenously), in these zero-salt and overnight-fasted rats, reduced LD J tCO2 values to normal. Further, infusion of losartan (5 mg/kg body wt, intravenously), the specific AII AT 1 receptor blocker, reduced J tCO2 in overnight-fasted rats by two-thirds (16 Ϯ 4 pmol/min и mm, P Ͻ 0.05). Finally, we perfused 10 Ϫ 11 M AII intraluminally with and without 10 Ϫ 6 M losartan: AII increased J tCO2 to 45 Ϯ 6 pmol/min и mm, equal to the zero-salt flux. This was completely abrogated by simultaneous losartan perfusion. Therefore, these results suggest that AII is an in vivo stimulator of late distal tubule bicarbonate reabsorption. ( J. Clin. Invest. 1996. 97:120-125.)

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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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In vivo modulation of rat distal tubule net HCO3 flux by VIP, isoproterenol, angiotensin II, and ADH

Cited by 24 publications

References 0 publications

Endothelin-Induced Increased Nitric Oxide Mediates Augmented Distal Nephron Acidification as a Result of Dietary Protein

Endothelin-Induced Increased Nitric Oxide Mediates Augmented Distal Nephron Acidification as a Result of Dietary Protein

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

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

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In vivo modulation of rat distal tubule net HCO3 flux by VIP, isoproterenol, angiotensin II, and ADH

Cited by 24 publications

References 0 publications

Endothelin-Induced Increased Nitric Oxide Mediates Augmented Distal Nephron Acidification as a Result of Dietary Protein

Endothelin-Induced Increased Nitric Oxide Mediates Augmented Distal Nephron Acidification as a Result of Dietary Protein

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

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

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