Dogmas and surprises about the renin-angiotensin system and sodium reabsorption.

After many years of studies on the renin–angiotensin system (RAS), one of the central concepts is that the RAS forms an effective defence mechanism against low-sodium states and hypotension. Low-perfusion pressure sensed by the afferent arteriole, low-distal delivery sensed by the macula densa and low blood pressure sensed by the sympathetic nervous system increase renin release, leading to angiotensin generation and sodium retention, vasoconstriction and restoration of blood pressure. About 15 years ago, the first reports appeared indicating angiotensin concentrations in the proximal tubule of higher magnitude than in the plasma [1,2]. Attempts to relate intraluminal angiotensin II (Ang II) concentrations to the functionality ascribed to the RAS were not very successful: the intratubular system did not seem to be adapting synchronously with the systemic RAS. What is the matter here? Is there a local RAS that acts independently from the systemic RAS? What would be the physiological relevance? In a recent article, Thomson et al. [3] explore the possibility that the local proximal tubular RAS functions in an opposite fashion to the systemic RAS: salt loading increased proximal tubular Ang II levels and sodium reabsorption. In this commentary, we attempt to place these recent findings in perspective with previous studies on the systemic and local RAS. The classical view: the RAS is a sodium-retaining mechanism