renal/urinary system
N |
• homozygotes exhibit a normal GFR on two levels of protein intake (4% and 40%), as measured by FITC-inulin clearance
• total renal blood flow is not significantly altered under baseline conditions
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• increased blood congestion in mutant kidneys, esp. in the renal medulla
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• in response to L-NAME infusion, homozygotes exhibit a greater % decrease (39%) in total renal blood flow relative to similarly-treated wild-type controls (27%)
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• under basal conditions on a 20% protein diet, 24-hr total urinary nitrate and nitrite excretion rates are more than double those in wild-type controls
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• on a high (40%) protein diet, homozygotes exhibit decreased urinary osmolality relative to wild-type controls
• after an 18-hr water restriction, homozygotes on either a 20% or 40% protein diet (but not a 4% protein diet) are unable to raise their maximal urinary osmolality above that noted under basal conditions
• however, no differences in osmolar excretion are observed on a high protein diet
• no decrease in aquaporin-2 or -3 expression is observed
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• fractional urea excretion is markedly increased on both the 4% and 40% protein diets relative to wild-type controls, reaching 102% of the filtered load on a 40% protein diet
• in contrast, fractional excretion rates of Na and K are not significantly altered
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• when normalized by brain weight, wet kidney weight is significantly reduced relative to that in wild-type controls
• however, no differences in cell number, cell type or morphology are observed
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• on a high (40%) protein diet, homozygotes exhibit a marked depletion of urea in the inner medulla relative to wild-type controls
• however, no differences in Na or K concentrations are observed in the cortex, outer medulla, or inner medulla
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• on a normal (20%) protein diet, homozygotes exhibit a significantly increased urine flow relative to wild-type controls
• on a high (40%) protein diet, homozygotes show a greater urine volume than wild-type controls, resulting in a marked reduction in the urine/plasma (U/P) inulin ratio
• after an 18-hr water restriction, homozygotes on either a 20% or 40% protein diet (but not a 4% protein diet) are unable to reduce their urine flow to levels below those observed under basal conditions
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• homozygotes exhibit a marked urinary concentrating defect due to a failure of urea transport from the inner medullary collecting duct lumen to the inner medullary interstitium, resulting in osmotic diuresis
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homeostasis/metabolism
N |
• under basal conditions (free access to water) on a 20% protein diet, normal plasma vasopressin levels are observed
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• on a high (40%) protein diet, homozygotes exhibit significantly lower plasma urea levels than wild-type controls
• in contrast, plasma concentrations of Na, K, and Cl are not significantly altered
|
• under basal conditions on a 20% protein diet, 24-hr total urinary nitrate and nitrite excretion rates are more than double those in wild-type controls
|
• on a high (40%) protein diet, homozygotes exhibit decreased urinary osmolality relative to wild-type controls
• after an 18-hr water restriction, homozygotes on either a 20% or 40% protein diet (but not a 4% protein diet) are unable to raise their maximal urinary osmolality above that noted under basal conditions
• however, no differences in osmolar excretion are observed on a high protein diet
• no decrease in aquaporin-2 or -3 expression is observed
|
• fractional urea excretion is markedly increased on both the 4% and 40% protein diets relative to wild-type controls, reaching 102% of the filtered load on a 40% protein diet
• in contrast, fractional excretion rates of Na and K are not significantly altered
|
behavior/neurological
• on a normal (20%) protein diet, homozygotes exhibit significantly greater fluid consumption than wild-type controls
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growth/size/body
• during an 18-hr water restriction, homozygotes on a 20% or 40% protein diet exhibit a body weight reduction of 18% and 24%, respectively
• however, no significant loss of body weight is noted after water restriction on a low (4%) protein diet
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cardiovascular system
• increased blood congestion in mutant kidneys, esp. in the renal medulla
|
• in response to L-NAME infusion, homozygotes exhibit a greater % decrease (39%) in total renal blood flow relative to similarly-treated wild-type controls (27%)
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reproductive system
• when normalized by brain weight, wet testis weight is significantly increased relative to that in wild-type controls
• however, no differences in cell number, cell type or morphology are observed
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endocrine/exocrine glands
• when normalized by brain weight, wet testis weight is significantly increased relative to that in wild-type controls
• however, no differences in cell number, cell type or morphology are observed
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