Kibble J D, Neal A M, Colledge W H, Green R, Taylor C J
Department of Biomedical Science, University of Sheffield, Sheffield S10 2TN, UK.
J Physiol. 2000 Jul 1;526 Pt 1(Pt 1):27-34. doi: 10.1111/j.1469-7793.2000.00027.x.
The aims of this study were to investigate (a) if renal Na(+) handling was normal in Cftr(tm2cam) delta F508 cystic fibrosis mice, (b) whether adaptation to dietary salt depletion was preserved and (c) whether Cftr(tm2cam) delta F508 mice exhibited enhanced amiloride-sensitive Na(+) absorption. In Na(+)-replete animals (maintained on a 0.32 % NaCl diet) given a 150 mM NaCl i.v. maintenance infusion, there was no difference in fractional Na(+) excretion (FE(Na)) between wild-type (0. 42 +/- 0.06 %, n = 12) and Cftr(tm2cam) delta F508 mice (0.47 +/- 0.13 %, n = 7). Amiloride infusion significantly increased FE(Na) in both wild-type (3.14 +/- 0.83 %, n = 6) and Cftr(tm2cam) delta F508 mice (3. 47 +/- 0.63 %, n = 9), though with no significant difference between genotypes. A 14 day dietary salt restriction (animals maintained on a 0.03 % NaCl diet) and maintenance infusion with a 15 mM NaCl vehicle caused a reduction in FE(Na) to 0.14 +/- 0.05 %, n = 8 in wild-type mice and 0.14 +/- 0.04 %, n = 8 in Cftr(tm2cam) delta F508 mice. No significant difference in the ability to adapt to low salt conditions was apparent comparing the two genotypes. Treatment of salt-restricted mice with amiloride resulted in a blunted natriuresis in both wild-type mice (FE(Na) = 1.10 +/- 0.16 %, n = 7) and Cftr(tm2cam) delta F508 mice (FE(Na) = 1.97 +/- 0.29 %, n = 9). The natriuresis induced by amiloride was significantly greater in Cftr(tm2cam) delta F508 mice than in wild-type controls. In conclusion, Cftr(tm2cam) delta F508 mice exhibit normal renal salt excretion when either salt replete or salt restricted. Enhanced amiloride-sensitive FE(Na) is consistent with increased Na(+) absorption via the amiloride-sensitive sodium channel ENaC, in cystic fibrosis kidney, but this was only observed during salt restriction.
(a) Cftr(tm2cam) delta F508囊性纤维化小鼠的肾脏钠处理是否正常；(b) 对饮食中盐分缺乏的适应性是否得以保留；(c) Cftr(tm2cam) delta F508小鼠是否表现出增强的氨氯地平敏感性钠吸收。在给予150 mM NaCl静脉维持输注的钠充足动物（维持在0.32% NaCl饮食）中，野生型小鼠（0.42±0.06%，n = 12）和Cftr(tm2cam) delta F508小鼠（0.47±0.13%，n = 7）之间的钠排泄分数（FE(Na)）没有差异。氨氯地平输注显著增加了野生型小鼠（3.14±0.83%，n = 6）和Cftr(tm2cam) delta F508小鼠（3.47±0.63%，n = 9）的FE(Na)，尽管不同基因型之间没有显著差异。14天的饮食盐分限制（动物维持在0.03% NaCl饮食）并用15 mM NaCl载体进行维持输注，导致野生型小鼠的FE(Na)降至0.14±0.05%，n = 8，Cftr(tm2cam) delta F508小鼠的FE(Na)降至0.14±0.04%，n = 8。比较两种基因型，在适应低盐条件的能力上没有明显差异。用氨氯地平处理盐分限制的小鼠，导致野生型小鼠（FE(Na)=1.10±0.16%，n = 7）和Cftr(tm2cam) delta F508小鼠（FE(Na)=1.97±0.29%，n = 9）的利钠作用减弱。Cftr(tm2cam) delta F508小鼠中氨氯地平诱导的利钠作用显著大于野生型对照。总之，Cftr(tm2cam) delta F508小鼠在钠充足或盐分限制时均表现出正常的肾脏排盐。增强的氨氯地平敏感性FE(Na)与囊性纤维化肾脏中通过氨氯地平敏感性钠通道ENaC增加的钠吸收一致，但这仅在盐分限制期间观察到。
