Control of renin secretion from kidneys with renin cell hyperplasia.

Control of renin secretion from kidneys with renin cell hyperplasia.
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肾素细胞增生对肾脏肾素分泌的控制

DOI:
10.1152/ajprenal.00536.2013
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发表时间:
2014
期刊:
American journal of physiology. Renal physiology
影响因子:
--
通讯作者:
Kurtz A
Kurtz A
中科院分区:
--
文献类型:
--
作者:
Kurt B;Karger C;Wagner C;Kurtz A

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在肾素-血管紧张素-醛固酮系统功能突变丧失的状态下,肾脏产生肾素细胞的强烈增生。这些额外的肾素细胞位于典型的肾小球旁区域外,主要位于肾小球前血管壁,最显著的是在传入小动脉周围的多层血管中。由于这些异位肾素细胞的功能行为尚不清楚,我们的目的是表征肾素细胞增生对肾脏分泌肾素的控制。作为模型,我们使用缺乏醛固酮合成酶的小鼠肾脏(As - / -小鼠),显示肾素mRNA和血浆肾素浓度升高10倍。在绝对水平上,离体AS - / -肾脏的肾素分泌比野生型肾脏增加了10倍以上。在相对水平上,β-肾上腺素能激活剂异丙肾上腺素或降低细胞外Ca2+浓度对肾素分泌的刺激在两种基因型之间非常相似。此外,两种基因型对ANG II和灌注压力的抑制作用相似。在AS - / -小鼠肾脏中,连接蛋白40的缺失减弱了肾素分泌的压力依赖性和低细胞外Ca2+对肾素分泌的刺激作用,与野生型小鼠相同。我们的研究结果表明,在发育过程中产生的肾素细胞和位于成人肾脏不同位置的肾素细胞之间具有高度的功能相似性。它们还表明,与肾素分泌控制相关的膜蛋白表达高度相似,如β1-肾上腺素能受体、ANG II型1受体和连接蛋白40。
In states of loss-of-function mutations of the renin-angiotensin-aldosterone system, kidneys develop a strong hyperplasia of renin-producing cells. Those additional renin cells are located outside the classic juxtaglomerular areas, mainly in the walls of preglomerular vessels and most prominently in multilayers surrounding afferent arterioles. Since the functional behavior of those ectopic renin cells is yet unknown, we aimed to characterize the control of renin secretion from kidneys with renin cell hyperplasia. As a model, we used kidneys from mice lacking aldosterone synthase (AS−/−mice), which displayed 10-fold elevations of renin mRNA and plasma renin concentrations. On the absolute level, renin secretion from isolated AS−/−kidneys was more than 10-fold increased over wild-type kidneys. On the relative level, the stimulation of renin secretion by the β-adrenergic activator isoproterenol or by lowering of the concentration of extracellular Ca2+was very similar between the two genotypes. In addition, the inhibitory effects of ANG II and of perfusion pressure were similar between the two genotypes. Deletion of connexin40 blunted the pressure dependency of renin secretion and the stimulatory effect of low extracellular Ca2+on renin secretion in the same manner in kidneys of AS−/−mice as in wild-type mice. Our findings suggest a high degree of functional similarity between renin cells originating during development and located at different positions in the adult kidney. They also suggest a high similarity in the expression of membrane proteins relevant for the control of renin secretion, such as β1-adrenergic receptors, ANG II type 1 receptors, and connexin40.
DOI: 10.1126/science.3306925
发表时间: 1987-09
期刊: Science
影响因子: 56.9
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通讯作者: O. Skøtt;J. Briggs
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发表时间: 2005
期刊: Journal of the American Society of Nephrology : JASN.
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DOI: 10.1007/s00424-012-1134-7
发表时间: 2013
期刊: Pflügers Archiv - European Journal of Physiology
影响因子: --
作者:
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DOI: 10.1007/s004410051085
发表时间: 1998
影响因子: 3.6
作者:
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通讯作者: O. Skøtt
DOI: 10.1038/sj.ki.5002423
发表时间: 2007-10-01
影响因子: 19.6
作者:
Krattinger, N.;Capponi, A.;Haefliger, J-A
通讯作者: Haefliger, J-A