Pathophysiological consequences of changes in the coupling ratio of Na,K-ATPase for renal sodium reabsorption and its implications for hypertension.
Pathophysiological consequences of changes in the coupling ratio of Na,K-ATPase for renal sodium reabsorption and its implications for hypertension.
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Na,K-ATP酶耦合比变化对肾钠重吸收的病理生理后果及其对高血压的影响。
DOI：
10.1161/01.hyp.27.2.219
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Hopfer,U
中科院分区：
文献类型：
--
作者：
Orosz,DE;Hopfer,U
Recent reports indicate that α1-Na,K-ATPase from Dahl salt-sensitive (DS) rats contains a glutamine for leucine substitution associated with increased Na-K coupling at unchanged maximal velocity. Genetic analyses suggest that α1-Na,K-ATPase is a potential hypertension gene. Therefore, we investigated whether renal Na+metabolism could constitute a pathophysiological link between the molecular/functional change in Na,K-ATPase and hypertension. We simulated the consequences of increased Na-K coupling on overall Na-bicarbonate reabsorption in a proximal tubular transport model that incorporates apical Na-H exchanger and basolateral Na-bicarbonate cotransporter, K+channel, and Na,K-ATPase. As expected, increases in the levels of the former three transport pathways yielded higher Na+reabsorption. In contrast, increases in the maximal velocity of the Na,K-ATPase with a normal 3:2 (Na-K) coupling ratio did not increase Na+reabsorption when apical Na-H exchange activity was limiting overall absorption. However, an increase in the Na-K coupling from 3:2 to 3:1, reported for the mutant α1-Na,K-ATPase in DS rats, was associated with greater Na+reabsorption. This increase is a consequence of lower cytosolic pH and secondary stimulation of the Na-H exchanger at its allosteric H+site. Decreased pH results from activation of Na-bicarbonate cotransport by Na,K-ATPase–dependent membrane hyperpolarization due to greater charge movement in 3:1 Na-K coupling. Thus, an increase in the Na-K coupling ratio results in an altered set point for cellular Na+metabolism, with higher sodium reabsorption at unchanged Na,K-ATPase levels. The simulations thereby lend support for a unifying explanation for the salt sensitivity of DS rats, which has been proposed to stem from a mutation in the α1-Na,K-ATPase.
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DOI：
--
发表时间：
1973
期刊：
Journal of Physiology
影响因子：
--
作者：
R. Garay;P. J. Garrahan
通讯作者：
P. J. Garrahan
兔近端肾小管上皮细胞系的发育和表征。
影响因子：
19.6
作者：
Romero,MF;Douglas,JG;Eckert,RL;Hopfer,U;Jacobberger,JW
通讯作者：
Jacobberger,JW
影响因子：
8.3
作者：
GARCIANDIA, A;LOPEZ, R;DIEZ, J
通讯作者：
DIEZ, J
绘制大鼠 2 号染色体上血压数量性状位点的图谱。
DOI：
10.1172/jci117341
发表时间：
1994
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
A. Deng;H. Dene;John P. Rapp
通讯作者：
John P. Rapp
Dahl 盐敏感大鼠α1 Na ,K( )-ATPase 基因的序列分析。
DOI：
10.1161/01.hyp.18.5.689
发表时间：
1991
期刊：
Hypertension (Dallas, Tex. : 1979)
影响因子：
--
作者：
Simonet,L;StLezin,E;Kurtz,TW
通讯作者：
Kurtz,TW