Regulation of small artery caliber by tone, SMC length adaptation and matrix remodeling: a model study

Small artery resistance is regulated by both tone and remodeling. These processes interact: They share mechanical stimuli, tone is a major drive for remodeling, and remodeling shifts active, cytoskeletal and matrix distension‐tension relations and thereby the relation between SMC contractile activation and vasoconstriction. In this theoretical study, a single‐vessel model was developed that integrates mechanosensitivity, tone control, and remodeling of SMC and the matrix. Tone was driven by shear stress, wall stress and extrinsic factors. SMC remodeling was based on regulation of cell length. Eutrophic matrix remodeling was implemented based on maintained constriction acting as a ‘mold’ during matrix turnover and cross‐linking. The model predicts vessel behavior to depend critically on the ratio of SMC length for optimal force and reference for cell length regulation. Cell length adaptation during maintained contraction in the absence of flow was an instable process, resulting in a vicious circle of inward remodeling and increasing SMC span, effectively strangling the vessel. Inclusion of flow and shear‐dependent dilation was needed to stabilize this process. This work is a first step in the integrative modeling that is required to truly understand regulation of resistance vessel caliber.