A multi-component model of the dynamics of salt-induced hypertension in Dahl-S rats.

Abstract

BackgroundIn 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 salt-induced 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.ResultsThe 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 salt-induced 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).ConclusionOur 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.