1 Aortic Pulse Pressure Homeostasis Emerges 2 from Physiologic Adaptation of Systemic Arteries 3 to Local Mechanical Stresses 4 5

38 Aortic pulse pressure arises from the interaction of the heart, the systemic arterial 39 system and peripheral microcirculations. The complex interaction between 40 hemodynamics and arterial remodeling precludes the ability to experimentally ascribe 41 changes in aortic pulse pressure to particular adaptive responses. Therefore, the purpose 42 of the present work was to use a human systemic arterial system model to test the 43 hypothesis that pulse pressure homeostasis can emerge from physiologic adaptation of 44 systemic arteries to local mechanical stresses. First we assumed a systemic arterial 45 system that had a realistic topology consisting of 121 arterial segments. Then the 46 relationships of pulsatile blood pressures and flows in arterial segments were 47 characterized by standard pulse transmission equations. Finally, each arterial segment 48 was assumed to remodel to local stresses following three simple rules: 1) increases in 49 endothelial shear stress increases radius, 2) increases in wall circumferential stress 50 increases wall thickness, and 3) increases in wall circumferential stress decreases wall 51 stiffness. Simulation of adaptation by iteratively calculating pulsatile hemodynamics, 52 mechanical stresses and vascular remodeling led to a general behavior in response to 53 mechanical perturbations: initial increases in pulse pressure led to increased arterial 54 compliances, and decreases in pulse pressure led to decreased compliances. 55 Consequently, vascular adaptation returned pulse pressures back towards baseline 56 conditions. This behavior manifested when modeling physiologic adaptive responses to 57 changes in cardiac output, changes in peripheral resistances, and changes in local arterial 58 radii. The present work thus revealed that pulse pressure homeostasis emerges from 59 physiologic adaptation of systemic arteries to local mechanical stresses. 60 61