Analysis Tools
homeostasis/metabolism
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• following bilateral renal ischemia-reperfusion injury, mice show significantly higher plasma creatinine levels than wild-type controls at 48 hours after reperfusion
• furosemide pretreatment reduces plasma creatinine levels in mutant males but not in wild-type controls
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• following bilateral renal ischemia-reperfusion injury, mice show a significantly higher elevation of blood urea nitrogen levels than wild-type controls at 24 hours and 48 hours after reperfusion
• pretreatment with furosemide 2 hours before ischemia ameliorates BUN levels in mutant males at 24 and 48 hours after reperfusion but has no effect in wild-type controls
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• kidney renin levels are slightly but significantly reduced relative to those in wild-type controls
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• whereas whole-kidney Na+ reabsorption (TNa) is normal, kidney oxygen consumption (QO2) is 80% higher, resulting in a nearly 40% lower TNa/ QO2 ratio relative to that in wild-type controls
• at baseline, intrarenal PO2 levels are lower in the outer medulla but normal in the cortex relative to wild-type controls
• after treatment with furosemide, mice show a 2.7-fold higher increase of PO2 levels in the outer medulla than wild-type controls, such that differences in PO2 levels are no longer significant
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• oxygen consumption in the kidneys is markedly increased, resulting in medullary hypoxia
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• mice are able to fully compensate for loss of paracellular Na+ transport in the proximal tubule by upregulating transcellular Na+ reabsorption in the thick ascending limb of Henle at the expense of increased oxygen consumption
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• following infusion with hypertonic saline (2% NaCl), mice show a higher urine Na+ excretion rate than similarly treated wild-type controls
• mice exhibit 40% greater natriuresis in response to furosemide (an NKCC2 blocker) than wild-type controls, consistent with increased activity of the Na-K-2Cl cotransporter NKCC2 in the thick ascending limb of Henle
• mice are able to maximally conserve Na+ and fully suppress urinary Na+ excretion by more than 90%, even on a diet of severe Na+ depletion (<0.01% Na+), similar to wild-type controls
• the diuretic response to hydrochlorothiazide (an NCC blocker) and benzamil (an ENaC blocker) is modestly but not significantly increased
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• following bilateral renal ischemia-reperfusion injury, mice show a significantly higher blood urea nitrogen levels and plasma creatinine levels and a larger area of ischemic injury than wild-type controls; almost all renal tubules (~95%) in the outer medulla exhibit ischemic injury, and tubule injury, esp. within proximal tubules, is also noted in parts of the renal cortex, unlike in wild-type controls where only ~50% of renal tubules in the outer medulla show morphological features of injury while the renal cortex remains almost intact
• pretreatment with furosemide significantly ameliorates the injury score in mutant males but has no significant effect in wild-type controls
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renal/urinary system
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• following infusion with hypertonic saline (2% NaCl), mice show a higher urine Na+ excretion rate than similarly treated wild-type controls
• mice exhibit 40% greater natriuresis in response to furosemide (an NKCC2 blocker) than wild-type controls, consistent with increased activity of the Na-K-2Cl cotransporter NKCC2 in the thick ascending limb of Henle
• mice are able to maximally conserve Na+ and fully suppress urinary Na+ excretion by more than 90%, even on a diet of severe Na+ depletion (<0.01% Na+), similar to wild-type controls
• the diuretic response to hydrochlorothiazide (an NCC blocker) and benzamil (an ENaC blocker) is modestly but not significantly increased
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• following bilateral renal ischemia-reperfusion injury, mice show a significantly higher blood urea nitrogen levels and plasma creatinine levels and a larger area of ischemic injury than wild-type controls; almost all renal tubules (~95%) in the outer medulla exhibit ischemic injury, and tubule injury, esp. within proximal tubules, is also noted in parts of the renal cortex, unlike in wild-type controls where only ~50% of renal tubules in the outer medulla show morphological features of injury while the renal cortex remains almost intact
• pretreatment with furosemide significantly ameliorates the injury score in mutant males but has no significant effect in wild-type controls
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• mice show upregulation of transcellular Na-K-2Cl (NKCC2) transport activity in the thick ascending limb of Henle
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• mice are able to fully compensate for loss of paracellular Na+ transport in the proximal tubule by upregulating transcellular Na+ reabsorption in the thick ascending limb of Henle at the expense of increased oxygen consumption
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