American journal of physiology. Renal physiology
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Am. J. Physiol. Renal Physiol. · Jan 2009
Urea and NaCl regulate UT-A1 urea transporter in opposing directions via TonEBP pathway during osmotic diuresis.
In our previous studies of varying osmotic diuresis, UT-A1 urea transporter increased when urine and inner medullary (IM) interstitial urea concentration decreased. The purposes of this study were to examine 1) whether IM interstitial tonicity changes with different urine urea concentrations during osmotic dieresis and 2) whether the same result occurs even if the total urinary solute is decreased. Rats were fed a 4% high-salt diet (HSD) or a 5% high-urea diet (HUD) for 2 wk and compared with the control rats fed a regular diet containing 1% NaCl. ⋯ The LSD rats had decreased UT-A1 and UT-A3 in both portions of the IM. CLC-K1 and TonEBP were unchanged by LPD or LSD. We conclude that changes in CLC-K1, UT-A1, UT-A3, and TonEBP play important roles in the renal response to osmotic diuresis in an attempt to minimize changes in plasma osmolality and maintain water homeostasis.
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Am. J. Physiol. Renal Physiol. · Jan 2009
Angiotensin II regulates V2 receptor and pAQP2 during ureteral obstruction.
Release of bilateral ureteral obstruction (BUO) is associated with nephrogenic diabetes insipidus (NDI) and a reduced abundance of the vasopressin-regulated aquaporins. To evaluate the role of the vasopressin type 2 receptor (V2R), we determined V2R abundance in kidneys from rats subjected to 24-h BUO or 24-h unilateral ureteral obstruction (UUO) followed by 48-h release. Because angiotensin II type 1 (AT1) receptor blockade attenuates postobstructive polyuria and aquaporin-2 (AQP2) downregulation, we examined the effect of AT1 receptor blockade on AQP2 phosphorylated at serine 256 (pS256-AQP2) and V2 receptor complex abundance in kidney inner medulla (IM). ⋯ AT1 receptor blockade attenuated V2R, pS256-AQP2, and G(s)alpha protein downregulation in IM and partially reversed the obstruction-induced inhibition of sodium fluoride- and forskolin-stimulated cAMP generation in inner medullary membrane fractions from BUO rats. In conclusion, V2R downregulation plays a pivotal role in development of NDI after release of BUO. In addition, we have shown that angiotensin II regulates the V2 receptor complex and pS256-AQP2 in postobstructive kidney IM, probably by stimulating cAMP generation.
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Am. J. Physiol. Renal Physiol. · Dec 2008
Role of p75NTR in female rat urinary bladder with cyclophosphamide-induced cystitis.
Previous studies demonstrated changes in urinary bladder neurotrophin content and upregulation of neurotrophin receptors, TrkA and the p75 neurotrophin receptor (p75(NTR)), in micturition reflex pathways after cyclophosphamide (CYP)-induced cystitis. p75(NTR) can bind nerve growth factor (NGF) and modulate NGF-TrkA binding and signaling. We examined p75(NTR) expression and the role of p75(NTR) in the micturition reflex in control and CYP-treated rats. p75(NTR) Immunoreactivity was present throughout the urinary bladder. CYP-induced cystitis (4 h, 48 h, chronic) increased (P < or = 0.05) p75(NTR) expression in whole urinary bladder as shown by Western blotting. ⋯ Intravesical instillation of PD90780 significantly (P < or = 0.01) reduced the volume threshold to elicit a micturition contraction in control rats (no inflammation) and CYP-treated in a closed urinary bladder system. These studies demonstrate 1) ubiquitous p75(NTR) expression in urinary bladder and increased expression with CYP-induced cystitis and 2) p75(NTR) blockade at the level of the urinary bladder produces bladder hyperreflexia in control and CYP-treated rats. The overall activity of the urinary bladder reflects the balance of NGF-p75(NTR) and NGF-TrkA signaling.
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Am. J. Physiol. Renal Physiol. · Dec 2008
Loop of Henle interaction with interstitial nodal spaces in the renal inner medulla.
Understanding dynamics of NaCl reabsorption from loops of Henle, and cellular and physiological consequences, requires a clear understanding of the structural relationships of loops with other functional elements of the inner medulla (IM). Pathways taken by ascending thin limbs (ATLs) and prebend segments along the corticopapillary axis were evaluated for the outer zone of the IM of the Munich-Wistar rat. Connectivity between these segments and microdomains of interstitium adjacent to collecting ducts (CDs) and abutting ascending vasa recta (interstitial nodal spaces) was assessed by evaluating their physical contacts. ⋯ The number of contacts made by the total population of prebend or postbend segments exhibits a marked, periodic increase and decrease as a function of depth below the OM-IM boundary; this number of contacts correlates with equivalent periodic changes in prebend number. Simulations of loop distribution indicate that small discontinuities in loop distribution contribute to periodic changes in prebend number. Convergence of IM loop bends within CD clusters likely plays an essential role in NaCl compartmentalization by promoting NaCl reabsorption near interstitial regions lying adjacent to CDs and ascending vasa recta.
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Am. J. Physiol. Renal Physiol. · Dec 2008
p53 regulates renal expression of HIF-1{alpha} and pVHL under physiological conditions and after ischemia-reperfusion injury.
Ischemia-reperfusion injury (IRI) is a common cause of acute kidney injury (AKI) and is characterized by widespread tubular and microvascular damage. The tumor suppressor p53 is upregulated after IRI and contributes to renal injury in part by promoting apoptosis. Acute, short-term inhibition of p53 with pifithrin-alpha conveys significant protection after IRI. ⋯ Finally, inhibition of p53 prevents the dramatic changes in Von Hippel-Lindau protein morphology and expression after IRI. We conclude that activation of p53 after IRI mitigates the concomitant activation of the protective HIF-1 pathway. Modulating the interactions between the p53 and HIF-1 pathway can provide novel options in the treatment of AKI.