Pharmacological modulation of the renin-angiotensin system by mathematical modeling.

Abstract

The renin-angiotensin system (RAS) is one of the most important systems in blood pressure homeostasis and pathogenesis of cardiovascular-renal diseases. When blood volume goes down, juxtaglomerular cells in the kidneys secrete renin. Renin stimulates the production of angiotensin I (Ang I), which is then converted to angiotensin II (Ang II). Angiotensin II causes blood vessels to constrict, resulting in increased blood pressure. If the renin angiotensin system is over active, blood pressure will be too high. Most hypotensive drugs are designed to block this system at different points in the pathway. In this study, we developed a mathematical model of the renin-angiotensin system to emulate the response of the renin-angiotensin system in humans. This model consists of a set of differential equations. Special attention is paid to the estimation of all the model parameters from reported experimental data. These equations allow us to model hypertensive and normotensive patients and pharmacotherapeutic approaches to treatment. We show dose-response curves of blood pressure and biochemical components of the renin-angiotensin system. Our results reproduce clinical outcomes. We conclude that mathematical modeling of RAS is a useful approach for gaining insight into the complexities of homeostatic control of arterial pressure and pharmacotherapeutics.