Renal bicarbonate reabsorption in the rat. III. Distal tubule perfusion study of load dependence and bicarbonate permeability.

Chan, Y. L.; Malnic, Gerhard; Giebisch, Gerhard

doi:10.1172/jci114255

Cited by 28 publications

(30 citation statements)

References 32 publications

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“…Fluid absorption was observed at all lumen bicarbonate concentrations and tended to decrease at higher bicarbonate concentrations in late distal tubules. Increased rates of bicarbonate absorption and transport saturation had also been observed in a previous rat microperfusion study in which the entire distal tubule was perfused (7). To test whether replacement ofthe gluconate could have lowered the luminal calcium concentration and thus effect bicarbonate transport, a perfusion experiment with Ca-free solution was also performed.…”

Section: Methodsmentioning

confidence: 65%

“…After anesthesia by 100 mg/kg Inactin (Byk-Gulden, Konstanz, Germany), rats were prepared for microperfusion as previously described (7,22). After performance of a tracheotomy, the left jugular vein was cannulated with two catheters, one for infusion of saline (0.9% NaCl) at a rate of 1.5 ml/h, the other for administering an additional 1 ml of saline during the surgical preparation.…”

Section: Methodsmentioning

confidence: 99%

“…The method used to measure total CO2 has been described previously and was carefully followed (4,7). Collected The solutions used in this study are given in Table I.…”

Section: Methodsmentioning

confidence: 99%

“…Most free-flow micropuncture studies (see reference 3) have demonstrated significant bicarbonate absorption along the cortical distal tubule ( 1-1 1 ). Distal tubule bicarbonate reabsorption has been reported to increase with the delivery of bicarbonate to the distal tubule (4), with distal tubule flow rate (7), and during potassium depletion (5). Bicarbonate absorption is reduced by carbonic anhydrase inhibitors and induction ofrespiratory alkalosis (1).…”

Section: Methodsmentioning

confidence: 99%

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Renal bicarbonate reabsorption in the rat. IV. Bicarbonate transport mechanisms in the early and late distal tubule.

Wang¹,

Malnic²,

Giebisch³

et al. 1993

J. Clin. Invest.

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Bicarbonate transport was studied in vivo by separate microperfusion experiments of early and late distal tubules. Total CO2 was measured by microcalorimetry and fluid absorption by 3H-inulin. Significant bicarbonate absorption was observed in all experimental conditions. Bicarbonate transport was loaddependent upon increasing the luminal bicarbonate concentration from 15 to 50 mM in both early and late distal tubule segments and remained constant at higher concentrations at a maximum rate of 100-110 pmol/min per mm. At low lumen bicarbonate concentrations (15 mM), higher rates of bicarbonate absorption were observed in early (32.9±4.57 pmol/min per mm) as compared to late distal tubules (10.7±3.1 pmol/ min per mm). Amiloride and ethyl-isopropylamiloride both inhibited early but not late distal tubule bicarbonate absorption whereas acetazolamide blocked bicarbonate transport in both tubule segments. Fluid absorption was significantly reduced in both tubule segments by amiloride but only in early distal tubules by ethyl-isopropylamiloride. Substitution of lumen chloride by gluconate increased bicarbonate absorption in late but not in early distal tubules. Bafilomycin Al, an inhibitor of HATPase, inhibited late and also early distal tubule bicarbonate absorption, the latter at higher concentration. After 8 d on a low K diet, bicarbonate absorption increased significantly in both early and late distal tubules. Schering compound 28080, a potent H-K ATPase inhibitor, completely blocked this increment of bicarbonate absorption in late but not in early distal tubule. The data suggest bicarbonate absorption via Na+-H+ exchange and H-ATPase in early, but only by amiloride-insensitive H' secretion (H-ATPase) in late distal tubules. The study also provides evidence for activation of K+-H+ exchange in late distal tubules of K depleted rats. Indirect evidence implies a component of chloride-dependent bicarbonate secretion in late distal tubules and suggests that net bicarbonate transport at this site results from bidirectional bicarbonate movement. (J. Clin.

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Section: Methodsmentioning

confidence: 65%

Section: Methodsmentioning

confidence: 99%

“…The method used to measure total CO2 has been described previously and was carefully followed (4,7). Collected The solutions used in this study are given in Table I.…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Renal bicarbonate reabsorption in the rat. IV. Bicarbonate transport mechanisms in the early and late distal tubule.

Wang¹,

Malnic²,

Giebisch³

et al. 1993

J. Clin. Invest.

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“…Consequently, renal endothelins play an important mediating role in the increased H ϩ secretion/decreased HCO 3 secretion components of augmented distal nephron acidification that is induced by these two models of augmented distal nephron acidification, dietary intake of mineral acid and of acid-producing proteins. The decreased distal nephron HCO 3 secretion that is induced by HiPro might help ameliorate the obligate HCO 3 secretion that occurs in response to increased fluid flows in this nephron segment (25) and thereby ameliorate the increased terminal and its components, HCO 3 and H ϩ secretion, by in vivo microperfusion in HiProϩbosentan-treated rats without and with N-nitro-l-arginine methyl ester (L-NAME) after 3 wk. Positive/ negative values indicate reabsorption/secretion, respectively.…”

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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Molecular Mechanisms and Regulation of Urinary Acidification

Kurtz

2014

Comprehensive Physiology

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The H+ concentration in human blood is kept within very narrow limits, ~ 40 nM, despite the fact that dietary metabolism generates acid and base loads that are added to the systemic circulation throughout the life of mammals. One of the primary functions of the kidney is to maintain the constancy of systemic acid-base chemistry. The kidney has evolved the capacity to regulate blood acidity by performing three key functions: 1) reabsorb HCO3− that is filtered through the glomeruli to prevent its excretion in the urine; 2) generate a sufficient quantity of new HCO3− to compensate for the loss of HCO3− resulting from dietary metabolic H+ loads and loss of HCO3− in the urea cycle; and 3) excrete HCO3− (or metabolizable organic anions) following a systemic base load. The ability of the kidney to perform these functions requires that various cell types throughout the nephron respond to changes in acid-base chemistry by modulating specific ion transport and/or metabolic processes in a coordinated fashion such that the urine and renal vein chemistry is altered appropriately. The purpose of the article is to provide the interested reader with a broad review of a field that began historically ~ 60 years ago with whole animal studies, and has evolved to where we are currently addressing questions related to kidney acid-base regulation at the single protein structure/function level.

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Renal bicarbonate reabsorption in the rat. III. Distal tubule perfusion study of load dependence and bicarbonate permeability.

Cited by 28 publications

References 32 publications

Renal bicarbonate reabsorption in the rat. IV. Bicarbonate transport mechanisms in the early and late distal tubule.

Renal bicarbonate reabsorption in the rat. IV. Bicarbonate transport mechanisms in the early and late distal tubule.

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

Molecular Mechanisms and Regulation of Urinary Acidification

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