Kidney function in mice lacking aldosterone
Kidney function in mice lacking aldosterone
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DOI：
10.1152/ajprenal.00257.2005
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发表时间：
2006-01-01
影响因子：
4.2
通讯作者：
Smithies, O
中科院分区：
文献类型：
--
作者：
Makhanova, N;Lee, G;Smithies, O
缺乏醛固酮的小鼠的肾功能。Am J Physiol肾生理学290：F61-F69,2006。2005年8月23日首次出版；DOI：10.1152/ajprenal.00257.2005。-为了探索醛固酮减少或缺乏的影响，我们在小鼠中干扰了醛固酮合成酶(AS)的编码基因，并研究了AS(+/+)、AS(+/-)和AS(-/-)小鼠的血压和肾功能。AS(+/-)小鼠血压正常，电解质或肾脏基因表达无异常，但尿量显著高于正常，尿渗透压显著低于正常。相比之下，AS(-/-)小鼠血压低，电解质平衡异常(血浆K+、Ca2+和Mg2+浓度升高，HCO3-和Cl-浓度下降，但血浆Na+水平无差异)，水代谢紊乱(尿量增加，尿渗透压降低，尿浓缩和稀释能力受损)。AS(+/-)小鼠缺乏醛固酮导致了几个代偿性变化：食物摄入量/体重比增加，血浆糖皮质激素浓度增加，肾素-血管紧张素系统强烈激活。AS(-/-)小鼠在肾素合成和释放显著增加的同时，致密黄斑环氧合酶-2(COX-2)表达增加。补盐后，血浆电解质浓度、肾脏肾素和COX-2水平接近野生型小鼠，但AS(-/-)小鼠的低血压并未得到纠正。因此，AS(-/-)小鼠缺乏醛固酮会导致远端肾单位Na+重吸收受损，血压降低，肾素-血管紧张素系统激活增强。我们的数据显示，这些异常的实质性纠正，除了低血压，高饮食盐不依赖于醛固酮。
Kidney function in mice lacking aldosterone. Am J Physiol Renal Physiol 290: F61-F69, 2006. First published August 23, 2005; doi:10.1152/ajprenal.00257.2005.- To explore the effects of decreased amounts or absence of aldosterone, we have disrupted the gene coding for aldosterone synthase (AS) in mice and investigated blood pressure and kidney function in AS (+/+), AS (+/-), and AS (-/-) mice. AS (+/-) mice have normal blood pressures and show no abnormalities in electrolytes or kidney gene expression, but they have significantly higher than normal urine volume and lower urine osmolality. In contrast, the AS (-/-) mice have low blood pressure, abnormal electrolyte homeostasis (increased plasma concentrations of K+, Ca2+, and Mg2+ and decreased concentrations of HCO3- and Cl- but no difference in the plasma Na+ level), and disturbances in water metabolism (higher urine output, decreased urine osmolality, and impaired urine concentrating and diluting ability). Absence of aldosterone in the AS (+/-) mice induced several compensatory changes: an increased food intake-to-body weight ratio, an elevated plasma concentration of glucocorticoids, and strong activation of the renin-angiotensin system. Parallel with the markedly increased synthesis and release of renin, the AS (-/-) mice showed increased expression of cyclooxygenase-2 (COX-2) in macula densa. On salt supplementation, plasma electrolyte concentrations and kidney renin and COX-2 levels became similar to those of wild-type mice, but the lower blood pressure of the AS (-/-) mice was not corrected. Thus absence of aldosterone in AS (-/-) mice results in impairment of Na+ reabsorption in the distal nephron, decreased blood pressure, and strong renin-angiontensin system activation. Our data show the substantial correction of these abnormalities, except the low blood pressure, by high dietary salt does not depend on aldosterone.