Vascular smooth muscle cell contraction and relaxation in the isolated aorta: a critical regulator of large artery compliance.

Guido R. Y. De Meyer,Cor E. Van Hove,Gilles W. De Keulenaer,Sofie De Moudt,Paul Fransen,Arthur J. A. Leloup

doi:10.14814/phy2.13934

Abstract

Over the past few decades, isometric contraction studies of isolated thoracic aorta segments have significantly contributed to our overall understanding of the active, contractile properties of aortic vascular smooth muscle cells (VSMCs) and their cross‐talk with endothelial cells. However, the physiological role of VSMC contraction or relaxation in the healthy aorta and its contribution to the pulse‐smoothening capacity of the aorta is currently unclear. Therefore, we investigated the acute effects of VSMC contraction and relaxation on the isobaric biomechanical properties of healthy mouse aorta. An in‐house developed set‐up was used to measure isobaric stiffness parameters of periodically stretched (10 Hz) aortic segments at an extended pressure range, while pharmacologically modulating VSMC tone and endothelial cell function. We found that the effects of α1‐adrenergic stimulation with phenylephrine on the pressure‐stiffness relationship varied in sensitivity, magnitude and direction, with the basal, unstimulated NO production by the endothelium playing a pivotal role. We also investigated how arterial disease affected this system by using the angiotensin‐II‐treated mouse. Our results show that isobaric stiffness was increased and that the aortic segments demonstrated a reduced capacity for modulating the pressure‐stiffness relationship. This suggests that not only increased isobaric stiffness at normal pressure, but also a reduced capacity of the VSMCs to limit the pressure‐associated increase in aortic stiffness, may contribute to the pathogenesis of this mouse model. Overall, this study provides more insight in how aortic VSMC tone affects the pressure‐dependency of aortic biomechanics at different physiological and pathological conditions.

Highlights

The isometric contraction of isolated thoracic aorta segments in response to pharmacological or mechanical stimulation has been extensively investigated over the past few decades
We previously reported that activation of vascular smooth muscle cells (VSMCs) increases isobaric stiffness in aortic segments of the mouse (Leloup et al 2016)
We assessed the interactions between VSMC tone, distending pressure and isobaric biomechanics of isolated mouse aortic segments

Summary

Introduction

The isometric contraction of isolated thoracic aorta segments in response to pharmacological or mechanical stimulation has been extensively investigated over the past few decades. Many studies have contributed significantly to our overall understanding of the local, humoral, mechanical, and neurogenic regulation of the molecular pathways involved in thoracic aorta vascular smooth muscle (VSMC) contraction and relaxation (Russell and Watts 2000; Fransen et al 2015; Leloup et al 2015). Dysfunction of these pathways has been shown to contribute to numerous pathologies, including hypertension and arterial stiffness (Wilkinson et al 2002; Lindesay et al 2010).

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