A dynamic model of angiotensin II infusion experiments.

Applications of control theory in studies of biological system dynamics have come to be called compartmental modelling. A second order, nonlinear, compartmental model is developed which describes the dynamics of the hormone angiotensin II (AII) and arterial blood pressure (BP) during AII infusion experiments. The model is partially identified using dose response data for constant infusion rates between 0.01 and 0.10 microgram/kg/min over a period of several minutes. This study represents a first step in understanding the dynamics of regulation of arterial blood pressure by the renin-angiotensin system. AII is a vasoconstrictor and is known to participate in the natural regulation of BP. AII is also believed to be an agent in the development of hypertension and atherosclerosis. The model is used to identify causal mechanisms which are consistent both with the established correlation between plasma AII concentration and arterial BP and with current physiological knowledge. The study demonstrates how a simple state variable model can be used to provide guidance concerning the design of future infusion experiments.

[1]  J. Blair‐West,et al.  A dose-response comparison of the actions of angiotensin II and angiotensin III in sheep. , 1980, Journal of Endocrinology.

[2]  V. Dzau Vascular renin-angiotensin: a possible autocrine or paracrine system in control of vascular function. , 1984, Journal of cardiovascular pharmacology.

[3]  Umberto Viaro,et al.  On the Relationship between Forrester's Schematics and Compartmental Graphs , 1986, IEEE Transactions on Systems, Man, and Cybernetics.

[4]  C. Rosenfeld,et al.  Metabolic clearance of angiotensin II in pregnant and nonpregnant sheep. , 1985, The American journal of physiology.

[5]  G. Fink,et al.  Effects of Chronic Intracerebroventricular Infusion of Angiotensin II on Arterial Pressure and Fluid Homeostasis , 1982, Hypertension.

[6]  R. Fraser,et al.  Angiotensin II, Aldosterone and Arterial Pressure: A Quantitative Approach Arthur C. Corcoran Memorial Lecture , 1979, Hypertension.

[7]  Claudio Cobelli,et al.  An expanded schematic for compartmental systems , 1986 .

[8]  C. Rosenfeld,et al.  The chronically instrumental ewe: a model for studying vascular reactivity to angiotensin II in pregnancy. , 1981, The Journal of clinical investigation.

[9]  J. Hall,et al.  Control of sodium excretion by angiotensin II: intrarenal mechanisms and blood pressure regulation. , 1986, The American journal of physiology.

[10]  Claudio Cobelli,et al.  Controllability, Observability and Structural Identifiability of Multi Input and Multi Output Biological Compartmental Systems , 1976, IEEE Transactions on Biomedical Engineering.

[11]  A. Coli,et al.  Metabolic clearance rate of radioiodinated angiotensin II in normal men. , 1972, The American journal of physiology.

[12]  G. Tregear,et al.  Reduction of blood clearance rate of [Val5]angiotensin II by [Sar1, Ile8]angiotensin II in sheep. , 1981, Life sciences.

[13]  R. F. Brown Compartmental System Analysis: State of the Art , 1980, IEEE Transactions on Biomedical Engineering.

[14]  D. Ganten,et al.  Plasma angiotensin II: dipsogenic levels and angiotensin-generating capacity of renin. , 1980, The American journal of physiology.

[15]  P. Weidmann,et al.  Blood pressure control in normotensive members of hypertensive families. , 1986, Kidney international.

[16]  I. Page,et al.  Angiotensin Tachyphylaxis and its Reversal , 1966, Circulation research.

[17]  K. Catt,et al.  The role of angiotensin II receptors in vascular regulation. , 1984, Journal of cardiovascular pharmacology.

[18]  R. Mulholland,et al.  Analysis of linear compartment models for ecosystems. , 1974, Journal of theoretical biology.

[19]  Keith Tizzard,et al.  Management System Dynamics , 1977 .

[20]  E. H. Twizell The mathematical modeling of metabolic and endocrine systems: E.R. Carson, C. Cobelli and L. Finkelstein John Wiley and Sons, Chichester, Sussex, UK, 394 pp., £45.15, 1983 , 1984 .

[21]  G. Fink,et al.  Hypertension during chronic peripheral and central infusion of angiotensin III. , 1985, The American journal of physiology.

[22]  E. Schiffrin,et al.  Vascular angiotensin II receptors in SHR. , 1984, Hypertension.

[23]  W. Pritchard,et al.  Production of hypertension and vascular disease by angiotensin. , 1966, Archives of pathology.