Abstract
The asserted dominant role of the kidneys in the chronic regulation of blood pressure and in the etiology of hypertension has been debated since the 1970s. At the center of the theory is the observation that the acute relationships between arterial pressure and urine production—the acute pressure-diuresis and pressure-natriuresis curves—physiologically adapt to perturbations in pressure and/or changes in the rate of salt and volume intake. These adaptations, modulated by various interacting neurohumoral mechanisms, result in chronic relationships between water and salt excretion and pressure that are much steeper than the acute relationships. While the view that renal function is the dominant controller of arterial pressure has been supported by computer models of the cardiovascular system known as the “Guyton-Coleman model”, no unambiguous description of a computer model capturing chronic adaptation of acute renal function in blood pressure control has been presented. Here, such a model is developed with the goals of: 1. capturing the relevant mechanisms in an identifiable mathematical model; 2. identifying model parameters using appropriate data; 3. validating model predictions in comparison to data; and 4. probing hypotheses regarding the long-term control of arterial pressure and the etiology of primary hypertension. The developed model reveals: long-term control of arterial blood pressure is primarily through the baroreflex arc and the renin-angiotensin system; and arterial stiffening provides a sufficient explanation for the etiology of primary hypertension associated with ageing. Furthermore, the model provides the first consistent explanation of the physiological response to chronic stimulation of the baroreflex.
Highlights
Theoretical analysis and observations of the control of blood volume and salt content by the kidneys has led to the hypothesis that arterial pressure is determined in the long-term by the balance between the level of salt intake and the acute relationship between pressure and salt excretion by the kidneys
Results 1: Response to volume infusion Guyton and colleagues conducted experiments in which a large amount of blood was infused into an anesthetized dog, resulting in a rapid increase in total blood volume of 45% compared to initial baseline value
The model captures physiological phenomena occurring on times scales ranging from milliseconds to days
Summary
Theoretical analysis and observations of the control of blood volume and salt content by the kidneys has led to the hypothesis that arterial pressure is determined in the long-term (over time scales of days or more) by the balance between the level of salt intake and the acute relationship between pressure and salt excretion by the kidneys. It is stated that the renal pressure/volume control system adjusts arterial pressure with “infinite gain” and that the renal function curve and rate of salt and water intake are the “two sole determinants of the long-term arterial pressure”[1]. While it is certain that at any steady level of arterial pressure the rates of salt and water intake and excretion are balanced, there is considerable debate over how this balance is achieved, and what are the long-term determinants of arterial pressure[2,3,4,5]. The Guyton-Coleman model cannot be used to explore alternative hypotheses
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