Commentary on ‘Current computational models do not reveal the importance of the nervous system in long‐term control of arterial pressure’

The long-term control of blood pressure has been recognized as a complex mixture of neural, hormonal and intrinsic factors involving the brain, heart, vasculature and especially the kidney. While computational modelling approaches to organ function have offered much promise recently (Hunter & Borg, 2003; Hunter et al. 2003), allowing researchers to test hypotheses or simulate stimuli difficult to assess experimentally, their application to blood pressure control has been somewhat limited. In 1972, Guyton and Coleman published a model which attempted to provide the basis for long-term blood pressure control (Guyton et al. 1972). This model, composed of hundreds of equations, has both baffled and intrigued legions of physiologists. The model has been somewhat updated to reflect recent advances (Guyton, 1990), although the role of the central nervous system is predominantly lacking. The central feature of the model is the linkage between blood pressure and sodium balance, where any imbalance between salt intake and excretion leads to a progressive alteration in the filling of the vascular system and thus changes in blood pressure. This in turn alters sodium excretion, a feature defined as the pressure–natriuresis relationship. A key aspect in this concept is that it puts the kidney at the very centre of long-term blood pressure control. This means that any chronic change in blood pressure must have been accompanied by an alteration in the pressure–natriuresis relationship. One effect of this model and concept has been to focus much research in hypertension on the kidney. More recently, this fundamental role of the kidney has become a source of renewed debate (Osborn, 2005; Osborn et al. 2005; Korner, 2007). The question has arisen as to whether the Guyton–Coleman model is still valid and can therefore form the basis of an updated model or whether it should be moved aside and a new structure built from the ground up. There is little doubt that the area has held itself back to some extent through the use of propriority modelling platforms and a failure to make the underlying code accessible. However, newer modelling tools, such as CMISS (www.cmiss.org) or Simulink in Matlab (www.mathworks.com), offer the prospect of providing an open-source platform for future modelling endeavours. This could allow multiple research groups to test and refine sections of the model in a collaborative nature. In this issue of Experimental Physiology, two opposing views are presented. Montani and Van Vliet (2009a,b) argue that the structure of the Guyton–Coleman model is fundamentally sound. Osborn and co-workers (2009a,b) argue that in light of the evidence for a major role of the sympathetic nervous system in long-term control of arterial pressure and the pathogenesis of hypertension, new mathematical models for long-term control of arterial pressure may be necessary. They argue that renal control of total blood volume is not the only factor that affects the long-term level of arterial pressure, that the Guyton–Coleman model overestimates the importance of renal control of body fluids and total blood volume in blood pressure regulation and that an alternative model can be developed in which sympathetic nervous system activity plays an important role in long-term control of arterial pressure independent of its effects on total blood volume. The aim in publishing these ‘Exchange of Views’ articles is to stimulate debate and encourage further research in this area. At the first cardiovascular control conference, held 4 years ago in Jaipur, India, it was proposed (Evans et al. 2005) that computational modelling held much promise for the area of long-term blood pressure control but it was also one with few research groups active. At the second meeting, held in December 2008 in Mamallapuram, India, the need