Smooth muscle tone alters arterial stiffness: the importance of the extracellular matrix to vascular smooth muscle stiffness ratio

Background: Recent studies show that vascular smooth muscle (VSM) is more important to elastic artery mechanics than previously believed. It remains unclear whether increased VSM tone increases or decreases arterial stiffness. Methods and results: We developed a novel arterial mechanics model based on pressure–diameter relationships that incorporates the contributions of extracellular matrix (ECM) and VSM to arterial stiffness measures. This model is advantageous because it simple enough to use with limited clinical data but has biologically relevant parameters which include ECM stiffness, VSM stiffness, and VSM tone. The model was used to retrospectively analyze the effects of nitroglycerin-induced vasodilation in four clinical studies. Stiffness parameters were modeled for five arterial regions including both elastic and muscular arteries. The model describes complex experimental data with changing VSM tone and blood pressure. Our analysis found that when ECM is less stiff than VSM, increasing VSM tone increases arterial stiffness. The opposite is seen when ECM is stiffer than VSM, increasing VSM tone decreases stiffness. Our results also suggest that VSM tone is a compensatory mechanism for elevated ECM stiffness in hypertensive individuals. Conclusion: Based on retrospective analysis of four clinical studies, we propose a simple hypothesis for the role of VSM tone on arterial stiffness: increased VSM tone increases arterial stiffness when VSM is stiffer than ECM and decreases arterial stiffness when ECM is stiffer than VSM. This hypothesis and the methods used in this study could have important implications for understanding arterial physiology in both hypertension and cardiovascular disease and deserve further exploration.