Reply from V. A. Averina, H. G. Othmer, G. D. Fink and J. W. Osborn

Abstract

The intent of our paper was not to formulate a comprehensive mathematical model of the relationship between salt intake, salt excretion and arterial pressure, but rather to point out that the experimentally and clinically observable relationships between these variables can be explained under more than one set of physiological assumptions. The regulation of sodium chloride excretion is quite complex and involves many known and apparently yet-to-be-discovered factors of which arterial pressure is only one (Reinhardt & Seeliger, 2000; Seeliger et al. 2004; Bie, 2009). We thank Drs Judge and Dorrington for their quite correct observation that alterations in angiotensin levels would normally occur in response to different salt intakes, and that the resulting influence on renal sodium excretion is not incorporated in the model. In a slightly more developed model than the one we presented this could easily be accounted for by appropriate adjustments of the time constant for reaching sodium balance (τSE in our eqn (6)). However, their point does not invalidate the fact that sodium balance is ultimately achieved even when angiotensin II levels are ‘clamped’ (Cowley & Skelton, 1991; Seeliger et al. 2004) due to the operation of other powerful factors that control sodium excretion (one of which is arterial pressure). It is also worth noting that plasma angiotensin II levels reach their nadir at surprising low daily salt intakes (Kjolby et al. 2005), and thus changes in angiotensin II cannot account for the ready achievement of sodium balance at higher daily sodium intakes (typical of most human populations today). Thus we remain convinced that there are multiple possible physiological explanations for the commonly observed relationships between arterial pressure and renal sodium excretion.