SimBiology

Systemic Renin-Angiotensin-System (RAS) Model

This document presents a SimBiology® model of the systemic Renin- Angiotensin-System as described in the book chapter, “Using a Systems Biology Approach to Explore Hypotheses Underlying Clinical Diversity of the Renin Angiotensin System and the Response to Antihypertensive Therapies.” by Arthur Lo et al.[1]

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Model Description

This SimBiology model implementation of the systemic Renin-Angiotensin-System was first developed by Lo et al. and used to investigate the effects of different RAS-modulating therapies. The RAS pathway is crucial for blood pressure and kidney function control as well as a range of other organism-wide functions. The model describes the enzymatic conversion of the precursor protein Angiotensinogen to Angiotensin I and its downstream products Angiotensin 1-7, Angiotensin II and Angiotensin IV. Key pathway effects are triggered by the association of Angiotensin II with the AT1-Receptor. A positive feedback loop connects the Angiotensin II–AT1-Receptor complex with the Angiotensinogen conversion (not shown in the diagram ). Enzymatic reactions are modeled as pseudo-unimolecular using enzymatic activities as reaction rates. Degradation reactions are described using protein half-life times. Drug pharmacodynamics are included in the model using the term (1-DrugEffect) , where DrugEffect follows a sigmoidal dependence on the Drug concentration, to modify the target enzyme activity.

Systemic Renin-Angiotensin-System (RAS) Model

References

[1] Lo, A., Beh, J., Leon, H. D., Hallow, M. K., Ramakrishna, R., Rodrigo, M., & Sarkar, A. (2011). Using a Systems Biology Approach to Explore Hypotheses Underlying Clinical Diversity of the Renin Angiotensin System and the Response to Antihypertensive Therapies. Clinical Trial Simulations, 1, 457–482.