An unexpected role for angiotensin II in the link between dietary salt and proximal reabsorption
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Research Article Nephrology

An unexpected role for angiotensin II in the link between dietary salt and proximal reabsorption

Abstract

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.

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Figure 2

Range of possible VLPs.

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Range of possible VLPs. The upper and lower bounds of each box correspon...
The upper and lower bounds of each box correspond to the values obtained at 0 and maximum TGF stimulation, respectively. The filled circle and error bars in the center of each box designate the mean ± SEM obtained by averaging the upper and lower bounds for VLP in each nephron. This is where a typical nephron operates in the hydropenic rat. Nephrons in volume-expanded rats tend to operate closer to the elbow of the TGF response, so the value assigned to the high-salt diet likely overestimates the ambient VLP. The main point of this figure is to illustrate the major impact that the high-salt diet would exert on VLP if it succeeded in suppressing tubular Ang II, which is seen by comparing standard diet to the high-salt diet plus losartan. *P < 0.05 versus high-salt after Bonferroni correction.