Analysis Tools
renal/urinary system
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• under baseline conditions, homozygotes display a significant reduction in Na+, K+ and fluid excretion relative to wild-type controls
• however, no significant differences are observed in baseline glomerular filtration rate (GFR), filtered load of Na+ or other kidney function variables relative to wild-type controls
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• under baseline conditions, homozygotes exhibit a significantly lower K+ excretion than wild-type controls
• although K+ excretion is not reduced to the extent seen in wild-type mice after enteral NaCl loading, it is decreased more in mutant than in wild-type mice after i.v. NaCl loading
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• under baseline conditions, homozygotes exhibit a significantly lower Na+ excretion than wild-type controls
• homozygotes display an impaired ability to excrete NaCl in the urine after an enteral load of NaCl due to increased tubular Na+ reabsorption
• however, intravenous administration of NaCl elicits a natriuresis equivalent to that of wild-type controls
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• homozygotes exhibit a significant reduction of cGMP levels in the mucosa of proximal jejunum and ileum, but not in colon, relative to wild-type controls
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• renal clearance measurements (GFR, filtered Na+ load, and Na+ excretion rate) indicate that homozygotes are impaired in their ability to respond to enteral NaCl loading by increased renal Na+ excretion
• however, no such differences are observed in response to i.v. NaCl loading
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digestive/alimentary system
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• homozygotes display an abolished short-circuit current (Isc) in the jejunum both in the presence or absence of ethyl isopropyl amiloride (EIPA), suggesting that jejunal electrogenic anion secretion is significantly reduced relative to wild-type controls
• in contrast, EIPA-sensitive, unidirectional sodium flux (used as an index of Na+/H+ exchanger-mediated Na+ absorption) in the jejunum is normal, and transepithelial tissue conductance (Gt) remains unaltered both in the presence and absence of EIPA relative to wild-type controls
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cardiovascular system
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• following telemeter implantation, recovery, and sequential administration of a normal (1%), low (0.01%), and high (5%) NaCl diet for at least 3 days on each diet, homozygotes have a significantly higher mean arterial blood pressure than wild-type controls under resting conditions, showing a consistent increase of 10-15 mmHg regardless of the salt content of the diet
• no significant difference in blood pressure response is observed between the two genotypes at 24 hrs after a sudden switch from a 0.01% NaCl to a 5% NaCl diet
• no significant differences are observed between genotypes in baseline blood pressure or in blood pressure responses to enteral or i.v. NaCl loading
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homeostasis/metabolism
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• under baseline conditions, homozygotes exhibit a significantly higher plasma Na+ concentration than wild-type controls
• in contrast, baseline plasma K+ concentration is similar to that in wild-type controls
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• under baseline conditions, homozygotes display a significant reduction in Na+, K+ and fluid excretion relative to wild-type controls
• however, no significant differences are observed in baseline glomerular filtration rate (GFR), filtered load of Na+ or other kidney function variables relative to wild-type controls
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• under baseline conditions, homozygotes exhibit a significantly lower K+ excretion than wild-type controls
• although K+ excretion is not reduced to the extent seen in wild-type mice after enteral NaCl loading, it is decreased more in mutant than in wild-type mice after i.v. NaCl loading
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• under baseline conditions, homozygotes exhibit a significantly lower Na+ excretion than wild-type controls
• homozygotes display an impaired ability to excrete NaCl in the urine after an enteral load of NaCl due to increased tubular Na+ reabsorption
• however, intravenous administration of NaCl elicits a natriuresis equivalent to that of wild-type controls
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