An unexpected role for angiotensin II in the link between dietary salt and proximal reabsorption.
An unexpected role for angiotensin II in the link between dietary salt and proximal reabsorption.
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DOI：
10.1172/jci26092
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发表时间：
2006-04
期刊：
影响因子：
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通讯作者：
S. Thomson;A. Deng;L. Wead;K. Richter;R. Blantz;V. Vallon
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文献类型：
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作者：
S. Thomson;A. Deng;L. Wead;K. Richter;R. Blantz;V. Vallon
我们着手证实长期持有但未经检验的假设，即膳食盐通过对肾素-血管紧张素系统的相互作用，以促进盐稳态的方式影响近端重吸收。 Wistar大鼠饲喂标准或高盐饮食7天，然后进行肾微穿刺以测定单肾单位GFR（SNGFR）和近端重吸收。肾小球反馈 (TGF) 系统被用作操纵 SNGFR 的工具，以便区分净近端重吸收 (Jprox) 的主要变化与肾小球小管平衡引起的变化。 Ang II 对 Jprox 的影响通过 Jprox 对 AT1 受体拮抗剂氯沙坦的敏感性来确定。通过放射免疫测定法测定血浆、整个肾脏和中近端小管液体的 Ang II 含量。在标准饮食的大鼠中，氯沙坦使 Jprox 降低 25%，并使 TGF 反应的最大范围降低 50%。高盐饮食抑制血浆和全肾血管紧张素II水平。但高盐饮食未能减少氯沙坦对 Jprox 或 TGF 反应的影响，反而导致肾小管液 Ang II 含量增加。 Ang II 对 Jprox 的持续作用阻止了高盐饮食引起的晚期近端血流量的大幅上升。这些观察结果挑战了传统模型，并表明近端肾小管 Ang II 在盐充足的大鼠中的作用是稳定肾单位功能，而不是促进盐稳态。
We set out to confirm the long-held, but untested, assumption that dietary salt affects proximal reabsorption through reciprocal effects on the renin-angiotensin system in a way that facilitates salt homeostasis. Wistar rats were fed standard or high-salt diets for 7 days and then subjected to renal micropuncture for determination of single-nephron GFR (SNGFR) and proximal reabsorption. The tubuloglomerular feedback (TGF) system was used as a tool to manipulate SNGFR in order to distinguish primary changes in net proximal reabsorption (Jprox) from changes due to glomerulotubular balance. The influence of Ang II over Jprox was determined by the sensitivity of Jprox to the AT1 receptor antagonist, losartan. Plasma, whole kidneys, and fluid from midproximal tubules were assayed for Ang II content by radioimmunoassay. In rats on the standard diet, losartan reduced Jprox by 25% and reduced the maximum range of the TGF response by 50%. The high-salt diet suppressed plasma and whole-kidney Ang II levels. But the high-salt diet failed to reduce the impact of losartan on Jprox or the TGF response and actually caused tubular fluid Ang II content to increase. The persistent effect of Ang II on Jprox prevented a major rise in late proximal flow rate in response to the high-salt diet. These observations challenge the traditional model and indicate that the role of proximal tubular Ang II in salt-replete rats is to stabilize nephron function rather than to contribute to salt homeostasis.