Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.

We present the current state of the development of the SAPHIR project (a Systems Approach for PHysiological Integration of Renal, cardiac and respiratory function). The aim is to provide an open-source multi-resolution modelling environment that will permit, at a practical level, a plug-and-play construction of integrated systems models using lumped-parameter components at the organ/tissue level while also allowing focus on cellular-or molecular-level detailed sub-models embedded in the larger core model. Thus, an in silico exploration of gene-to-organ-to-organism scenarios will be possible, while keeping computation time manageable. As a first prototype implementation in this environment, we describe a core model of human physiology targeting the short-and long-term regulation of blood pressure, body fluids and homeostasis of the major solutes. In tandem with the development of the core models, the project involves database implementation and ontology development.

No abstract

In 50 normotensive controls, the increase in erythrocyte Na+ concentration up to 12.4 k 2.0 mmol/l cells (mean & SD) ensures half-maximal stimulation of outward Na+,K+ cotransport fluxes. Fortysix out of sixty-five patients with essential hypertension required more than 16 mmol/l cells of internal Na+ concentration to obtain a similar effect, strongly suggesting an abnormal cotransport function.Seven out of fourteen hypertensive patients with normal Na,K cotransport function showed Na+ ,Li+ countertransport fluxes higher than the normal upper limit of 220 pmol (1 cells h)-'. Conversely, countertransport fluxes were normal in fourteen hypertensives with abnormal cotransport function.The above results indicate that the total population of patients with essential hypertension is heterogenous and includes one subgroup of subjects with abnormal Na+,K+ cotransport function, and another with increased Na+,Li + countertransport fluxes.