Limited urinary concentration and damaged tubules in rats with a syngeneic kidney graft

Michimata, Mari; Wang, Weihua; Fujita, Sayuri; Mizutani, Hiroya; Fujimori, Keisei; Satoh, Susumu; Ohta, Makoto; Ito, Sadayoshi; Kimura, Tokihisa; Araki, Tsutomu; Imai, Yutaka; Matsubara, Mitsunobu

doi:10.1046/j.1523-1755.2001.060002672.x

Cited by 12 publications

(37 citation statements)

References 27 publications

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“…This however, is highly unlikely, because expression, activity, and regulation of transporters was selectively unaffected, reduced, or augmented. In another syngeneic rat kidney transplantation model without rejection, limited urinary concentrating ability and tubular damage was also reported (14). Ischemia after transplantation could be considered as a cause of delayed graft function (19,38), but ischemia/ reperfusion results in a different pattern of changes in expression levels of renal transporters and receptors compared with the present findings.…”

Section: Discussionsupporting

confidence: 69%

“…Non-immunologic factors are increasingly regarded as important for the prognosis of the transplant. In humans, investigations of changes on the tubular level are hardly possible, and only a few functional studies in animals are available (12)(13)(14)(15)(16)(17)(18)(19)(20). No direct data exist on expression and function of transporters and receptors involved in transport after renal transplantation.…”

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confidence: 99%

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Renal Transplantation Modulates Expression and Function of Receptors and Transporters of Rat Proximal Tubules

Velić¹,

Hirsch²,

Bartel³

et al. 2004

Journal of the American Society of Nephrology

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Abstract. Kidney transplantation often leads to disturbances of solute and volume maintenance in humans. To investigate underlying mechanisms, expression and function of renal transporters and receptors of the proximal tubule (PT) were analyzed in an acute rejection model of rat kidney transplantation. Semiquantitative RT-PCR and Western blot, histology, immunohistochemistry, and microfluorometry were performed on whole kidneys and isolated PT. With acute rejection, Na ϩ / H ϩ -exchanger type-3 (NHE-3) was markedly downregulated. Na ϩ -HCO 3 Ϫ -cotransporter (NBC-1) and Na ϩ -glucose transporter type-2 (SGLT2) were upregulated after transplantation. Expressions of Na ϩ /H ϩ -exchanger type-1 (NHE-1), Na ϩ /K ϩ -ATPase (NKA), angiotensin II (AngII) receptor (AT-1), or natriuretic peptide receptor (GC-A) were unaltered. Microfluorometric analyses of intracellular pH, Na ϩ , and Ca 2ϩ demonstrated a decrease in NHE-3 function and AngII-mediated stimulation of NHE-3. AngII-mediated inhibition of NHE-1 and function of all other transporters tested remained unaltered. Function of AT-1 and GC-A were unaffected. Reduced expression of NHE-3 was also confirmed by semiquantitative immunohistochemistry. These findings suggest that expression and function of transmembrane proteins involved in Na ϩ -transport after transplantation and rejection is specifically modulated. The local renin-angiotensin-system is apparently not altered.

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Section: Discussionsupporting

confidence: 69%

mentioning

confidence: 99%

Renal Transplantation Modulates Expression and Function of Receptors and Transporters of Rat Proximal Tubules

Velić¹,

Hirsch²,

Bartel³

et al. 2004

Journal of the American Society of Nephrology

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“…Dehydration, which promotes AVP secretion, produces the maximal urinary concentration by enhancing the expression of both AQP2 and rat BSC1 (rBSC1) [10, 15, 16, 17]. We have demonstrated that dehydration markedly increases AQP2 mRNA expression [18], consistent with a dehydration-induced increase in protein synthesis [19].…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, an examination of the expression of AQP2 in the dehydrated condition, which induces a small but significant urinary concentrating ability even in CRF rat [7], may reveal some of the mechanisms underlying the residual urinary concentrating ability in CRF. The present study is designed to investigate AQP2 expression in a rat model for CRF, in which regulation of rBSC1 expression in response to a reduction of nephron number [17]and to dehydration [16]is almost completely impaired [7]. …”

Section: Introductionmentioning

confidence: 99%

Residual Urinary Concentrating Ability and AQP2 Expression in a Rat Model for Chronic Renal Failure

Suzuki

Hatano²,

Michimata³

et al. 2004

Nephron Physiol

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Background: In chronic renal failure (CRF), a defect in urinary concentrating ability develops gradually as the renal failure progresses. Although several molecular mechanisms associated with renal urinary concentration are reported to be impaired in a rat model for renal failure, the mechanisms underlying residual urinary concentration ability in CRF remain to be elucidated. Methods: Rats that underwent an 8-week recovery period after 5/6 nephrectomy were used as the model for CRF. Urinary concentration was induced by 24-hour water restriction. Plasma osmolality and arginine vasopressin (AVP) were measured from blood sampled by inserting a catheter into the femoral artery before and after the water restriction. AQP2 mRNA expression in the inner medulla was examined by competitive PCR and in situ hybridization, and protein expression, by Western blotting. Rats that underwent sham operation were used as control. Results: Water restriction significantly reduced urine volume and increased urine osmolality in CRF rats, although such changes were much less than those in sham-operated rats. Plasma AVP was elevated at the basal condition, and further elevation was noted after water restriction. AQP2 mRNA signals were significantly intensified by water restriction even in CRF rats, although the increase was limited as in the case of urine osmolality. Western blotting also showed a small but significant enhancement of protein signals in response to water restriction in CRF rats. Conclusions: We noted a weak but significant response of AQP2 expression to dehydration in CRF rats. This response in the collecting duct may be one of the factors contributing to residual urinary concentrating ability in CRF.

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“…27) The molecular cloning of BSC1 14) has enabled us to investigate the expression of this transporter. 5) We ex amined BSC1 expression in a normal rat kidney that achieved maximal urinary concentration in the de hydrated condition, 5) a kidney isograft (a rat with kidney transplantation), 7) and a remnant kidney after 5/6 nephrectomy (a rat model for chronic renal failure), 8) the latter two of which lost the ability to perform maximal urinary concentration even in the dehydrated condition. A marked increase in BSC1 ex pression was observed in the normal kidney from the dehydrated rat 5) and not the kidney isograft 7) or the remnant kidney 8) (Fig.…”

Section: Regulation Of Sodium Transport and Bsc1 Expres Sion In Talmentioning

confidence: 99%

Renal Sodium Handling for Body Fluid Maintenance and Blood Pressure Regulation

Matsubara

2004

YAKUGAKU ZASSHI

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Renal sodium handling is an essential physiologic function in mammal for body uid maintenance and blood pres sure regulation. Recent advances in molecular biology have led to the identication of kidneyspecic sodium transport ers in the renal tubule, thereby supplying vast information for renal physiology as well as systemic physiology. Renal uri nary concentration for body uid maintenance is accomplished by counter current multiplication in the distal tubule. So dium transport in the thick ascending limb of Henle (TAL) is the initial process of this system. We have demonstrated that renal urinary concentration is regulated in part by the expression of the Na { _ K { _ 2Cl | cotransporter (BSC1) in TAL, by showing two mechanisms of BSC1 expression: pitressin vasopressin (AVP)dependent and AVPindependent mechanisms. Two additional ndings, namely, a lack of the ability to increase BSC1 expression leads to urinary concen trating defect and an enhanced BSC1 expression underlies the edemaforming condition, conrm the close association between sodium handling in TAL and body uid accumulation. The lines of evidence from our genetic studies of the general Japanese population suggest the importance of mendelian hypertension genes in the genetic investigation of es sential hypertension. Because those genes directly or indirectly regulate sodium transport by the Na_ Cl cotransporter or the epithelial sodium channel in the distal convoluted tubule to the collecting duct (distal tubular segments after TAL), sodium handling in this part of the renal tubule may be, at least in part, involved in blood pressure regulation. The un veiling of such physiologic roles of sodium handling based on the sodium transporters or on the tubular segments may lead to a better understanding of systemic physiology as well as to the development of novel therapy for body uid or blood pressure disorders.

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Limited urinary concentration and damaged tubules in rats with a syngeneic kidney graft

Cited by 12 publications

References 27 publications

Renal Transplantation Modulates Expression and Function of Receptors and Transporters of Rat Proximal Tubules

Renal Transplantation Modulates Expression and Function of Receptors and Transporters of Rat Proximal Tubules

Residual Urinary Concentrating Ability and AQP2 Expression in a Rat Model for Chronic Renal Failure

Renal Sodium Handling for Body Fluid Maintenance and Blood Pressure Regulation

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