Na,K-ATPase Activity in Renal Tubule Cells From Milan Hypertensive Rats

Melzi, Maria-Luisa; Bertorello, Alejandro M.; Fukuda, Yutaka; Muldin, Ingrid; Sereni, F; Aperia, Anita

doi:10.1093/ajh/2.7.563

Cited by 35 publications

(16 citation statements)

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“…15 Na ϩ /K ϩ -ATPase activity was also found enhanced in the medullary tissue of Milan hypertensive rats. 17 Similarly, glucose increases O 2 consumption and Na ϩ /H ϩ -exchanger activity in proximal tubules of diabetic rat models 16 and stimulates the baseline activity of the Na ϩ /K ϩ -ATPase pump in renal tubules, including mTAL. 18 It is believed to be the major substrate driving oxygen consumption and production of ATP and Na ϩ /K ϩ -ATPase related activity in mTAL.…”

Section: ·؊ Productionmentioning

confidence: 98%

Renal Oxidative Stress in Medullary Thick Ascending Limbs Produced by Elevated NaCl and Glucose

Mori

Cowley

2004

Hypertension

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Abstract-The effects of NaCl, glucose, and thyroid hormone on the production of superoxide (O 2 ·Ϫ ) within the renal medulla of Sprague-Dawley rats were examined. Responses of intracellular superoxide [O 2 ·Ϫ ] i in isolated medullary thick ascending limbs (mTALs) were studied using real-time fluorescent microscopy with measurement of the dehydroethidium (DHE) to ethidium (Eth) conversion ratio (Eth/DHE ratio unit). The results demonstrated that elevations of extracellular NaCl (from 152 to 252 mmol/L), D-glucose (from 5 to 25 mmol/L), and triiodo-thyronine (T3; 10 mol/L) significantly increased [

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Section: ·؊ Productionmentioning

confidence: 98%

Renal Oxidative Stress in Medullary Thick Ascending Limbs Produced by Elevated NaCl and Glucose

Mori

Cowley

2004

Hypertension

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“…Which is the true GFR in MHS and MNS? When the two results were incorporated within the framework of the other results obtained by studying the cellular response to osmotic pressure (59) and the tubular function measured in isolated kidneys (121,122) in isolated tubular cells (101) or in cell membranes prepared from these kidneys (52,72), it is clear that the GFR is elevated in MHS.…”

Section: Personal Approachmentioning

confidence: 99%

Genetic variations of tubular sodium reabsorption leading to “primary” hypertension: from gene polymorphism to clinical symptoms

Bianchi

2005

American Journal of Physiology-Regulatory, Integrative and Comp

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Bianchi, Giuseppe. Genetic variations of tubular sodium reabsorption leading to "primary" hypertension: from gene polymorphism to clinical symptoms. Am J Physiol Regul Integr Comp Physiol 289: R1536-R1549, 2005. doi:10.1152/ajpregu.00441.2005.-The definition of the most appropriate strategy to demonstrate causation of a given geneticmolecular mechanism in a complex multifactorial polygenic disease like hypertension is hampered by the underestimation of the complexity arising from the genetic and environmental interactions. To disentangle this complexity, we developed a strategy based on six steps: 1) isolation of a rodent model of hypertension (Milan hypertensive strain and Milan normotensive strain) that shares some pathophysiological abnormalities with human primary hypertension; 2) definition in the model of the sequence of events linking these abnormalities to a genetic molecular mechanism; 3) determination of the polymorphism of the three adducin genes discovered in the model both in rats and in humans; 4) comparison at biochemical and physiological levels between the rodent models and the hypertensive carriers of the "mutated" gene variants; 5) evaluation of the impact of the adducin genes in hypertension and its organ complications with association and linkage studies in humans, also considering the genetic and environmental interactions; and 6) development of a pharmacogenomic approach aimed at establishing the therapeutic benefit of a drug interfering with the sequence of events triggered by adducin and their effect's size. The bulk of data obtained demonstrates the importance of a multidisciplinary approach considering a variety of genetic and environmental interactions. Adducin functions within the cells as a heterodimer composed of a combination of three subunits. Each of these subunits is coded by genes mapping to different chromosomes. Therefore, the interaction among these genes, taken together with the interactions with other modulatory genes or with the environment, is indispensable to establish the adducin clinical impact. The hypothesis that adducin polymorphism favors the development of hypertension via an increased tubular sodium reabsorption is well supported by a series of consistent experimental and clinical data. Many mechanistic aspects, underlying the link between these genes and clinical symptoms, need to be clarified. The clinical effect size of adducin must be established also with the contribution of pharmacogenomics with a drug that selectively interferes with the sequence of events triggered by the mutated adducin.genes; blood pressure; Na-K pump; Na channel; adducin The difficulty lies, not only in the new ideas, but in escaping the old ones. J. M. Keynes STARLING'S LONG-LASTING concern was to use physiology as a means to bring basic science to the bedside. Indeed, by integrating the capillary fluid exchange with the cardiac pump function, Starling provided a substantial contribution to bridge the gap between the contemporary basic science of circulation and the clinical sympto...

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“…A large deal of these experiments were carried out in a strain of genetically hypertensive rats (MHS, Milan hypertensive strain) 1 that we developed along with their normotensive controls (MNS, Milan normotensive strain) (1). These studies, based on experimental procedures like MHS/MNS kidney cross-transplantation (2, 3), renal function measurements performed both in isolated kidneys (4,5) and in intact animals (6,7) as well as in whole cells (8,9) and cell membranes (10,11), indicated that the primary defect leading to MHS hypertension was a faster ion transport rate across tubular cells (1). As the same transmembrane ion transport differences between MHS and MNS were also found in erythrocytes (1), these cells were used to demonstrate that the MHS abnormalities were genetically determined within the stem cells and genetically associated to hypertension (12).…”

Section: Introductionmentioning

confidence: 99%

Hypertension-associated point mutations in the adducin alpha and beta subunits affect actin cytoskeleton and ion transport.

Tripodi¹,

Valtorta²,

Torielli³

et al. 1996

J. Clin. Invest.

243

196

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The adducin heterodimer is a protein affecting the assembly of the actin-based cytoskeleton. Point mutations in rat adducin ␣ ( F316Y ) and ␤ ( Q529R ) subunits are involved in a form of rat primary hypertension (MHS) associated with faster kidney tubular ion transport. A role for adducin in human primary hypertension has also been suggested. By studying the interaction of actin with purified normal and mutated adducin in a cell-free system and the actin assembly in rat kidney epithelial cells (NRK-52E) transfected with mutated rat adducin cDNA, we show that the adducin isoforms differentially modulate: ( a ) actin assembly both in a cell-free system and within transfected cells; ( b ) topography of ␣ V integrin together with focal contact proteins; and ( c ) Na-K pump activity at V max (faster with the mutated isoforms, 1281 Ϯ 90 vs 841 Ϯ 30 nmol K/ h · mg pt., P Ͻ 0.0001). This co-modulation suggests a role for adducin in the constitutive capacity of the epithelia both to transport ions and to expose adhesion molecules. These findings may also lead to the understanding of the relation between adducin polymorphism and blood pressure and to the development of new approaches to the study of hypertension-associated organ damage. ( J. Clin. Invest. 1996. 97:2815-2822.)

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Na,K-ATPase Activity in Renal Tubule Cells From Milan Hypertensive Rats

Cited by 35 publications

References 0 publications

Renal Oxidative Stress in Medullary Thick Ascending Limbs Produced by Elevated NaCl and Glucose

Renal Oxidative Stress in Medullary Thick Ascending Limbs Produced by Elevated NaCl and Glucose

Genetic variations of tubular sodium reabsorption leading to “primary” hypertension: from gene polymorphism to clinical symptoms

Hypertension-associated point mutations in the adducin alpha and beta subunits affect actin cytoskeleton and ion transport.

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