McLoone, Violeta I. and Ringwood, John V. and Van Vliet, Bruce N.
A multi-component model of the dynamics of salt-induced
hypertension in Dahl-S rats.
BMC Physiology, 9 (20).
Background: In humans, salt intake has been suggested to influence blood pressure (BP) on a
wide range of time scales ranging from several hours or days to many months or years. Detailed
time course data collected in the Dahl salt-sensitive rat strain suggest that the development of saltinduced
hypertension may consist of several distinct phases or components that differ in their
timing and reversibility. To better understand these components, the present study sought to
model the dynamics of salt-induced hypertension in the Dahl salt sensitive (Dahl-S) rat using 3 sets
of time course data.
Results: The first component of the model (“Acute-Reversible”) consisted of a linear transfer
function to account for the rapid and reversible effects of salt on BP (ie. acute salt sensitivity,
corresponding with a depressed slope of the chronic pressure natriuresis relationship). For the
second component (“Progressive-Irreversible”), an integrator function was used to represent the
relatively slow, progressive, and irreversible effect of high salt intake on BP (corresponding with a
progressive salt-induced shift of the chronic pressure natriuresis relationship to higher BP levels).
A third component (“Progressive-Reversible”) consisted of an effect of high salt intake to
progressively increase the acute salt-sensitivity of BP (ie. reduce the slope of the chronic pressure
natriuresis relationship), amounting to a slow and progressive, yet reversible, component of saltinduced
hypertension. While the 3 component model was limited in its ability to follow the BP
response to rapid and/or brief transitions in salt intake, it was able to accurately follow the slower
steady state components of salt-induced BP changes. This model exhibited low values of mean
absolute error (1.92 ± 0.23, 2.13 ± 0.37, 2.03 ± 0.3 mmHg for data sets 1 - 3), and its overall
performance was significantly improved over that of an initial model having only 2 components. The
3 component model performed well when applied to data from hybrids of Dahl salt sensitive and
Dahl salt resistant rats in which salt sensitivity varied greatly in its extent and character (mean
absolute error = 1.11 ± 0.08 mmHg).
Conclusion: Our results suggest that the slow process of development of salt-induced
hypertension in Dahl-S rats over a period of many weeks can be well represented by a
combination of three components that differ in their timing, reversibility, and their associated effect
on the chronic pressure natriuresis relationship. These components are important to distinguish
since each may represent a unique set of underlying mechanisms of salt-induced hypertension.
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