Translational Research: Multi-Scale Models of the Pulmonary Circulation in Health and Disease - Multiscale Computer Modeling in Biomechanics and Biomedical Engineering - page 278

of airway reactivity, as dose-response to methacholine challenge is a standard test for
quantifying asthma severity. However in VSM the relevant stimuli are the partial
pressures of O 2 and CO 2 , and nitric oxide (NO) release via endothelial sensing of
shear stress. The multi-scale model for the airways is focused on explaining
pathology (airway hyper-responsiveness, a hallmark of asthma) whereas under-
standing the dynamics of VSM in the pulmonary circulation is necessary simply to
explain the normal function of the lung. That is, PO 2 -mediated vasoconstriction and
NO-mediated vasodilation operate simultaneously in the normal lung, with their
balance (along with other signaling pathways) determining the local VSM tension.
Transitioning the organ- and vessel-level models for the pulmonary circulation to
studies of e.g. pulmonary hypertension, where wall remodeling may be a significant
component, will require a multi-scale approach that spans to cellular signaling.

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