A Quantitative Systems Physiology Model of Renal Function and Blood Pressure Regulation: Application in Salt-Sensitive Hypertension

Figures

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  Figure 1. (a) Steady‐state MAP and GFR over a 10‐fold range of daily Na intake rates, for different strengths of the tubular pressure‐natriuresis mechanism (SP‐N). The strength of this mechanism determines the stability of mean arterial pressure and GFR as salt‐intake changes. In other words, impairment of this mechanism results in salt‐sensitive MAP and GFR. For this simulation, all other parameters, including effects of the RAAS, were set to the values given in the companion article for this simulation. (b) Steady‐state MAP and GFR over a 10‐fold range of Na intake rates, with and without the physiologic effects of the RAAS included in the model. (SP‐N = 3 for these simulations, all other parameters set to values in companion article). Removal of RAAS results in moderate salt‐sensitivity even when the tubular pressure‐natriuresis mechanism is strong.

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  Figure 2. Comparison of simulated outputs and clinical data for several variables of renal function. SS and SR VPs were simulated on a low sodium diet (60 mmol/day) for 3 days, followed by habitual sodium intake levels observed in Barba et al. (200 mmol/day) for 3 days (panel 1, dashed black line). The tubular pressure natriuresis strength (SP‐N) was estimated for each VP, constrained by the observed changes in MAP (panel 2). Other variables (panels 3–8) were then simulated and compared with clinical data. Solid lines: simulation; points with error bars: data from Barba et al.18

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  Figure 3. Simulated effect of salt‐sensitive status on blood pressure reduction and other functional variables with common antihypertensive classes. The simulations predict lower MAP reduction with ACEi, greater MAP reduction with diuretics, and similar MAP reduction with CCBs in SS compared to SR. The model also predicts that both ACEi and diuretics will lower glomerular pressure (and degree of reductions with ACEi is not different between SS and SR), while CCBs will not affect steady‐state glomerular pressure.