Acta Biotheoretica

, Volume 58, Issue 2–3, pp 143–170

A Computational Model of the Circulating Renin-Angiotensin System and Blood Pressure Regulation

Regular Article

DOI: 10.1007/s10441-010-9098-5

Cite this article as:
Guillaud, F. & Hannaert, P. Acta Biotheor (2010) 58: 143. doi:10.1007/s10441-010-9098-5

Abstract

The renin-angiotensin system (RAS) is critical in sodium and blood pressure (BP) regulation, and in cardiovascular-renal (CVR) diseases and therapeutics. As a contribution to SAPHIR project, we present a realistic computer model of renin production and circulating RAS, integrated into Guyton’s circulatory model (GCM). Juxtaglomerular apparatus, JGA, and Plasma modules were implemented in C ++/M2SL (Multi-formalism Multi-resolution Simulation Library) for fusion with GCM. Matlab© optimization toolboxes were used for parameter identification. In JGA, renin production and granular cells recruitment (GCR) are controlled by perfusion pressure (PP), macula densa (MD), angiotensin II (Ang II), and renal sympathetic activity (RSNA). In Plasma, renin and ACE (angiotensin-converting enzyme) activities are integrated to yield Ang I and II. Model vs. data deviation is given as normalized root mean squared error (nRMSE; n points). Identification: JGA and Plasma parameters were identified against selected experimental data. After fusion with GCM: (1) GCR parameters were identified against Laragh’s PRA-natriuresis nomogram; (2) Renin production parameters were identified against two sets of data ([renin] transients vs. ACE or renin inhibition). Finally, GCR parameters were re-identified vs. Laragh’s nomogram (nRMSE 8%, n = 9). Validation: (1) model BP, PRA and [Ang II] are within reported ranges, and respond physiologically to sodium intake; (2) short-term Ang II infusion induces reported rise in BP and PRA. The modeled circulating RAS, in interaction with an integrated CVR, exhibits a realistic response to BP control maneuvers. This construction will allow for modelling hypertensive and CVR patients, including salt-sensitivity, polymorphisms, and pharmacotherapeutics.

Keywords

Renin-angiotensin system Blood pressure Sodium Body fluids Kidney Juxtaglomerular apparatus Models (theoretical) 

Abbreviations

ACE

Angiotensin converting enzyme, ACE-1 (EC 3.4.15.1)

AGT

Angiotensinogen

Ang I (/II)

Angiotensin I (/II)

ATP

Adenosine triphosphate

AT1-R

Ang II type 1 receptor

BRENDA

BRaunschweig ENzyme DAtabase (http://www.brenda-enzymes.org/)

cAMP

Cyclic adenosine monophosphate

GC

Renin-secreting granular cells

GCM

Guyton’s circulatory model

JGA

Juxta-glomerular apparatus

MAP

Mean arterial pressure

MD

Macula densa

M2SL

Multi-formalism Multi-resolution Simulation Library

NID

Na input rate variable in Guyton’s circulatory model

PP

Perfusion pressure

PRA

Plasma renin activity

RAS

Renin-angiotensin system

RAAS

Renin-angiotensin-aldosterone system

Renin

(EC 3.4.23.15)

RSNA

Renal sympathetic nerve activity

SAPHIR [project]

A systems approach for physiological integration of renal, cardiac and respiratory functions

Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  1. 1.Inserm U927, CHU La MilétriePoitiersFrance

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