Increasing pulse pressure ex vivo, mimicking acute physical exercise, induces smooth muscle cell-mediated de-stiffening of murine aortic segments.

The mechanisms by which physical activity affects cardiovascular function and physiology are complex and multifactorial. In the present study, cardiac output during rest or acute physical activity was simulated in isolated aortic segments of healthy C57BL/6J wild-type mice. This was performed using the Rodent Oscillatory Tension Set-up to study Arterial Compliance (ROTSAC) by applying cyclic stretch of different amplitude, duration and frequency in well-controlled and manageable experimental conditions. Our data show that vascular smooth muscle cells (VSMCs) of the aorta have the intrinsic ability to "de-stiffen" or "relax" after periods of high cyclic stretch and to "re-stiffen" slowly thereafter upon return to normal distension pressures. Thereby, certain conditions have to be fulfilled: 1) VSMC contraction and repetitive stretching (loading/unloading cycles) are a prerequisite to induce post-exercise de-stiffening; 2) one bout of high cyclic stretch is enough to induce de- and re-stiffening. Aortic de-stiffening was highly dependent on cyclic stretch amplitude and on the manner and timing of contraction with probable involvement of focal adhesion phosphorylation/activation. Results of this study may have implications for the therapeutic potential of regular and acute physical activity and its role in the prevention and/or treatment of cardiovascular disease.