Proximal tubular function in adult rats treated neonatally with enalapril

Guron,; Nilsson, Mats; Leyssac,; Sundelin,; Friberg,

doi:10.1046/j.1365-201x.1998.00404.x

Cited by 14 publications

(10 citation statements)

References 22 publications

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“…Above that value, the proximal tubule glucose transport system is saturated and Ͼ1% of filtered glucose is delivered downstream. This predicted value is in accordance with measured values of the glucosuria threshold in the rat kidney under normal conditions, which range from 12 mM (17) to slightly Ͻ20 mM (13,19). Note that the glucosuria threshold is higher in diabetic rats (21).…”

Section: Impact Of Glucose Transport and Metabolismsupporting

confidence: 76%

Modeling oxygen consumption in the proximal tubule: effects of NHE and SGLT2 inhibition

Layton

Vallon

Edwards

2015

American Journal of Physiology-Renal Physiology

122

128

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Layton AT, Vallon V, Edwards A. Modeling oxygen consumption in the proximal tubule: effects of NHE and SGLT2 inhibition. Am J Physiol Renal Physiol 308: F1343-F1357, 2015. First published April 8, 2015 doi:10.1152/ajprenal.00007.2015.-The objective of this study was to investigate how physiological, pharmacological, and pathological conditions that alter sodium reabsorption (T Na) in the proximal tubule affect oxygen consumption (QO 2 ) and Na ϩ transport efficiency (TNa/QO 2 ). To do so, we expanded a mathematical model of solute transport in the proximal tubule of the rat kidney. The model represents compliant S1, S2, and S3 segments and accounts for their specific apical and basolateral transporters. Sodium is reabsorbed transcellularly, via apical Na ϩ /H ϩ exchangers (NHE) and Na ϩ -glucose (SGLT) cotransporters, and paracellularly. Our results suggest that TNa/QO 2 is 80% higher in S3 than in S1-S2 segments, due to the greater contribution of the passive paracellular pathway to TNa in the former segment. Inhibition of NHE or Na-K-ATPase reduced T Na and QO 2 , as well as Na ϩ transport efficiency. SGLT2 inhibition also reduced proximal tubular T Na but increased QO 2 ; these effects were relatively more pronounced in the S3 vs. the S1-S2 segments. Diabetes increased TNa and QO 2 and reduced TNa/QO 2 , owing mostly to hyperfiltration. Since SGLT2 inhibition lowers diabetic hyperfiltration, the net effect on TNa, QO 2 , and Na ϩ transport efficiency in the proximal tubule will largely depend on the individual extent to which glomerular filtration rate is lowered. sodium transport; glucose; metabolism; diabetes DESPITE INTENSE RESEARCH, the mechanisms underlying the development of chronic kidney diseases remain incompletely understood. Renal hypoxia is thought to be a unifying pathway to chronic kidney disease (15) and, in general, is due to a mismatch between changes in renal oxygen delivery and oxygen consumption (8). Oxygen consumption in the kidney serves in large part to actively reabsorb Na ϩ . Since the proximal tubule is where more than half the filtered load of Na ϩ is reabsorbed, the goal of this study was to investigate how physiological and pathological changes in sodium transport alter O 2 consumption in the proximal tubule.Sodium reabsorption along the proximal tubule is coupled to HCO 3 Ϫ and Cl Ϫ transport: early NaHCO 3 reabsorption raises the luminal concentration of Cl Ϫ and enhances the driving force for paracellular NaCl reabsorption in the later part of the tubule. Notably, changes in O 2 consumption (Q O 2 ) do not always correlate positively with changes in Na ϩ reabsorption. Deng et al. (4) observed that blocking carbonic anhydrase with benzolamide (a proximal tubule diuretic) lowered the energy efficiency of Na ϩ reabsorption in the kidney, as it simultaneously decreased net Na ϩ reabsorption and increased overall O 2 consumption. These effects were abolished by drugs that suppress Na ϩ /H ϩ exchange or basolateral Na ϩ -HCO 3 Ϫ cotransport. Deng et al. (4) surmised that benzolamide...

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Section: Impact Of Glucose Transport and Metabolismsupporting

confidence: 76%

Modeling oxygen consumption in the proximal tubule: effects of NHE and SGLT2 inhibition

Layton

Vallon

Edwards

2015

American Journal of Physiology-Renal Physiology

122

128

View full text Add to dashboard Cite

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“…It has been suggested that THP forms a highly negatively charged, hydrophobic, gelatinous barrier in the TALH that may decrease transepithelial electrolyte flux (42). If this was the case, the AT 1 receptor inhibitor-induced anomalous overproduction of THP in developing TALH cells could hamper solute reabsorption in the TALH and lead to sodium loss, as observed in adult rats subjected to neonatal RAS inhibition (7,9). Although our present study does not demonstrate the physiological role of THP, it suggests a causative link between RAS and THP expression during nephrogenesis.…”

Section: Discussioncontrasting

confidence: 50%

Neonatal RAS inhibition changes the phenotype of the developing thick ascending limb of Henle

Lasaitiene¹,

Friberg²,

Sundelin³

et al. 2004

American Journal of Physiology-Renal Physiology

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Pharmacological interruption of angiotensin II type 1 (AT(1)) receptor signaling during nephrogenesis in rats perturbs renal tubular development. Perturbed tubulogenesis may contribute to long-term impairment of urinary concentrating ability, which is the main functional irreversible defect. The aim of this study was to further characterize tubular developmental deficits in neonatal rats, focusing on the thick ascending limb of Henle (TALH), known to undergo profound developmental changes and to be involved in urine-concentrating mechanisms. We have carried out immunohistochemistry and Western immunoblotting using antibodies directed against the major histocompatibility complex class II (MHC II) molecule and different TALH-specific markers, namely, cyclooxygenase-2 (COX-2), Tamm-Horsfall glycoprotein (THP), and the bumetanide-sensitive Na(+)-K(+)-2Cl(-) cotransporter (BSC-1/NKCC2). Immunohistochemistry demonstrated expression of MHC II, COX-2, THP, and BSC-1/NKCC2 proteins in normally developing TALH cells. The AT(1)-receptor antagonist losartan abolished MHC II expression exclusively in the developing TALH cells. Increased expression of COX-2 and THP was observed in the TALH cells of losartan-treated rats. Western immunoblotting confirmed increases in cortical and medullary COX-2 and THP abundance and revealed a decrease in cortical BSC-1/NKCC2 abundance in response to losartan treatment. We conclude that neonatal losartan treatment causes significant changes in the phenotype of the developing TALH in the rat.

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“…2), indicating that the reduction in T c H 2 O could not be explained by a decreased NaCl delivery to the ascending limb of Henle’s loop. Moreover, we have recently been able to demonstrate that fluid flow rate at the end of the proximal straight segment actually tends to be elevated in adult rats treated neonatally with enalapril ( Guron et al . 1998b ).…”

Section: Discussionmentioning

confidence: 98%

Mechanisms of impaired urinary concentrating ability in adult rats treated neonatally with enalapril

Guron¹,

Nilsson²,

Nitescu³

et al. 1999

Acta Physiologica Scandinavica

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Neonatal angiotensin-converting enzyme inhibition or angiotensin II type-1 receptor blockade induces irreversible renal histological abnormalities and an impaired urinary concentrating ability in the rat. The aim of the present study was to determine the pathophysiological mechanisms underlying the defect in urine concentration in adult rats treated neonatally with enalapril. Male Wistar rats received daily intraperitoneal injections of enalapril (10 mg kg(-1)) or saline vehicle from 3 to 24 days of age. Assessments of fluid handling and maximal urine osmolality (Uosm(max)), renal function and tubular free water reabsorption (T(c)H2O) under pentobarbital anaesthesia, renal tissue solute concentrations, renal aquaporin-2 (AQP2) expression, and kidney histology, were performed in 12-16-week-old rats. Uosm(max) (1488 +/- 109 vs. 2858 +/- 116 mosm kg(-1), P < 0.05) and maximal T(c)H2O were reduced in enalapril- vs. vehicle-treated rats after administration of 1-desamino-8-D-arginine vasopressin. Neonatally enalapril-treated rats showed marked papillary atrophy, a decrease in medullary tissue solute concentrations, and a reduction in AQP2 expression specifically in the inner medulla. Glomerular filtration rate, renal plasma flow and urinary excretion rates of sodium, potassium and chloride did not differ between groups. In conclusion, adult rats treated neonatally with enalapril showed a urinary concentrating defect of renal origin which primarily could be explained by the papillary atrophy. However, an impaired ability to generate medullary interstitial hypertonicity, and a decrease in inner medullary AQP2 expression, also seem to contribute to this defect.

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Proximal tubular function in adult rats treated neonatally with enalapril

Cited by 14 publications

References 22 publications

Modeling oxygen consumption in the proximal tubule: effects of NHE and SGLT2 inhibition

Modeling oxygen consumption in the proximal tubule: effects of NHE and SGLT2 inhibition

Neonatal RAS inhibition changes the phenotype of the developing thick ascending limb of Henle

Mechanisms of impaired urinary concentrating ability in adult rats treated neonatally with enalapril

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