A high-salt diet paradoxically increased proximal tubular fluid Ang II content and failed to reduce the impact of losartan on proximal reabsorption, indicating that tubular Ang II stabilizes nephron function.
Contrary to the traditional model, dietary salt loading increases proximal tubular Ang II content to stabilize nephron function rather than contributing to salt homeostasis.
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.
Scott C. Thomson (2006) studied Salt homeostasis (n=23). High-salt diet and Losartan vs. Standard diet was evaluated on Proximal reabsorption (Jprox) and tubular fluid Ang II content. A high-salt diet paradoxically increased proximal tubular fluid Ang II content and failed to reduce the impact of losartan on proximal reabsorption, indicating that tubular Ang II stabilizes nephron function.