Angiotensin-independent mechanism for aldosterone synthesis during chronic extracellular fluid volume depletion.
Angiotensin-independent mechanism for aldosterone synthesis during chronic extracellular fluid volume depletion.
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DOI：
10.1172/jci119249
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发表时间：
1997-03
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影响因子：
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通讯作者：
S. Okubo;F. Niimura;H. Nishimura;F. Takemoto;A. Fogo;T. Matsusaka;I. Ichikawa
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文献类型：
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作者：
S. Okubo;F. Niimura;H. Nishimura;F. Takemoto;A. Fogo;T. Matsusaka;I. Ichikawa
将野生型（Agt+/+）和纯合型血管紧张素原缺失突变体（Agt-/-）同窝仔置于正常（NS）或低Na饮食（LS）2周。NS期间血浆醛固酮水平（P（aldo））相当，在Agt+/+和Agt-/-的LS期间也类似地升高。此外，在两者中，P（aldo）的升高伴随着肾上腺皮质小球细胞和肾上腺P450 aldo mRNA的显著增加。Agt-/-小鼠与Agt+/+小鼠的区别在于其较高的血浆K水平，NS和LS期间分别约为1.5和3.8 mEq/L。在Agt-/-组中，P（aldo）与血浆K成正比。通过观察到K限制的叠加导致Agt+/+小鼠低血压和Agt-/-小鼠均匀死亡沿着P（aldo）分别降低75%和90%，证实了K在饮食Na限制期间对醛固酮增多症的重要性。因此，抑制钾，而不是血管紧张素，导致显着衰减高醛固酮症在饮食钠限制。因此，（a）LS期间存在强有力的不依赖于血管紧张素的机制用于醛固酮增多症;（B）高K是该机制的中心组分;（c）与目前的信念相反，高K对醛固酮合成和释放的紧张作用不需要完整的肾素-血管紧张素系统;和（d）通常，用于醛固酮增多症的中间反馈信号，即，低血压和高钾都被醛固酮作用有效地掩盖。
Wild-type (Agt+/+) and homozygous angiotensinogen deletion mutant (Agt-/-) littermates were placed on normal (NS) or low Na diet (LS) for 2 weeks. Plasma aldosterone levels (P(aldo)) were comparable during NS, and similarly elevated during LS in Agt+/+ and Agt-/-. Moreover, in both, the elevation in P(aldo) was accompanied by marked increase in adrenal zona glomerulosa cells and adrenal P450aldo mRNA. Agt-/- mice were distinguished from Agt+/+ mice by their higher plasma K level, by approximately 1.5 and approximately 3.8 mEq/liter during NS and LS, respectively. Within the Agt-/- group, P(aldo) was directly proportional to plasma K. The importance of K for the hyperaldosteronism during dietary Na restriction was verified by the observation that superimposition of K restriction led to hypotension in Agt+/+ and uniform death in Agt-/- mice along with a reduction in P(aldo) by 75 and 90%, respectively. Thus, suppression of potassium, but not angiotensin, led to a marked attenuation of hyperaldosteronism during dietary Na restriction. Therefore, (a) a powerful angiotensin-independent mechanism exists for the hyperaldosteronism during LS; (b) high K is a central component of this mechanism; (c) contrary to current belief, the tonic effect of high K on aldosterone synthesis and release does not require an intact renin-angiotensin system; and (d) normally, intermediary feedback signals for hyperaldosteronism, i.e., both hypotension and high K, are effectively masked by aldosterone actions.