Vascular aging impairs active modulation of murine aortic stiffness by smooth muscle cells

Aging causes changes to arterial contractility and tissue microstructure, resulting in arterial stiffening, a strong risk factor for cardiovascular diseases. Because the interaction between these effects is largely unexplored, this study aims to investigate how aging-induced changes in contractility and wall constituent microstructure impact arterial biomechanics in murine aortas. Vasoreactive responses of thoracic descending aortas of adult (5-mo-old, <i>n</i> = 5) and old (24-mo-old, <i>n</i> = 5) C57Bl/6J mice to phenylephrine, <i>N</i>^ω-nitro-l-arginine methyl ester (l-NAME), and sodium nitroprusside were measured under dynamic pressurization conditions. Whole vessel and individual-constituent biaxial viscoelastic properties were characterized during contraction and relaxation while mimicking physiological dynamic loading conditions. In addition, elastin fibers, collagen fibers, and smooth muscle nuclei microstructural organization and morphological properties were quantified in pressurized aortas using two-photon laser scanning microscopy. Compared with adult mice, aortas of old mice displayed thicker walls but similar pressure-diameter behaviors in the absence of contraction. Vasoconstriction in aortas of adult mice <i>1</i>) significantly increased wall thickness, <i>2</i>) reduced pulse wave velocity at physiologically high pressure ranges, <i>3</i>) reduced circumferential and axial stresses and stiffnesses, and <i>4</i>) altered constituent load bearing. Conversely, aortas of old mice exhibited reduced contractility, altered vasoreactive responses, and reduced cell density. As a result, they were uncapable to alter any of their biomechanical properties through vasoconstriction. In conclusion, vasoconstriction enables modulation of axial and circumferential stresses and stiffnesses in the adult mouse aorta. With aging, this modulatory capacity was impaired.<b>NEW & NOTEWORTHY</b> Using a biaxial pressure myograph that mimics physiological loading conditions, this study demonstrates the capacity of vascular smooth muscle cells in male C57BL/6J mice at 5 mo of age to modulate aortic stiffness through vasoconstriction and dilation. In addition, this capacity is shown to be lost in male C57BL/6J mice at 24 mo of age.