Loop analysis of blood pressure/volume homeostasis

We performed a mathematical analysis of the dynamic control loops regulating the vasomotor tone of vascular smooth muscle, blood volume, and mean arterial pressure, which involve the arginine vasopressin (AVP) system, the atrial natriuretic peptide system (ANP), and the renin-angiotensin-aldosterone system (RAAS). Our loop analysis of the AVP-ANP-RAAS system revealed the concurrent presence of two different regulatory mechanisms, which perform the same qualitative function: one affects blood pressure by regulating vasoconstriction, the other by regulating blood volume. Both the systems are candidate oscillators consisting of the negative-feedback loop of a monotone system: they admit a single equilibrium that can either be stable or give rise to oscillatory instability. Also a subsystem, which includes ANP and AVP stimulation of vascular smooth muscle cells, turns out to be a candidate oscillator composed of a monotone system with multiple negative feedback loops, and we show that its oscillatory potential is higher when the delays along all feedback loops are comparable. Our results give insight into the physiological mechanisms ruling long-term homeostasis of blood hydraulic parameters, which operate based on dynamical loops of interactions.Author summary: The efficiency and resilience of our body are guaranteed by the presence of myriads of dynamic control loops that regulate fundamental vital functions. In this work, we studied the regulatory mechanisms that govern the interplay of vasoconstriction/vasodilation, blood volume and mean arterial pressure. We analysed the loops in the system and showed the presence of two coexisting mechanisms for blood pressure regulation, which perform the same qualitative function, conferring robustness to the system: one mechanism tunes vasoconstriction, the other blood volume. We showed that both systems are candidate oscillators: either they are stable or they oscillate regularly around their unique equilibrium. We analysed a subsystem that describes the stimulation of vascular smooth muscle cells due to the hormones arginine vasopressin (AVP) and atrial natriuretic peptide (ANP): also this system is a candidate oscillator ruled by multiple negative-feedback loops, and its potential for oscillations is higher when all the loops have similar delay. Our results cast light on the fundamental physiological phenomena that preserve the stable functioning of blood pressure and volume. This could have even wider relevance if other homeostasis and endocrine systems displayed similar features, with repercussions on the management of adverse homeostasis shifts like hypertension.