Isolated Vascular Smooth Muscle Stiffness as a Common Mechanism to the Increased Aortic Stiffness of Aging and Hypertension

Abstract

Increased vascular stiffness is common to both hypertension and aging, and is thought to be due to changes in the extracellular matrix. We have previously found that aortic stiffness was increased in the aorta of aging monkeys, and that isolated vascular smooth muscle cell (VSMC) stiffness, as assessed by atomic force microscopy (AFM), was increased from 12.8±0.3 kPa to 41.7±0.5 kPa. To determine whether this was unique to aging, we examined aortic stiffness in spontaneously hypertensive rats (SHR). In SHR, mean aortic pressure (123±4 mmHg) was increased compared to control Wistar‐Kyotos (96±6 mmHg), as did in vivo aortic stiffness (7.65 mm/ms versus 3.27 mm/ms). In order to determine if a component occurred at the level of the VSMC, we used AFM nanoindentation to measure VSMC stiffness, and also found it increased in SHR compared to WKY (29.2 kPa versus 13.8 kPa). This suggests that increased stiffness is not simply due to changes in the extracellular matrix, but an important component occurs at the level of VSMCs. Since this mechanism is observed in both aging and hypertension, it appears that it is a general mechanism mediating increased vascular stiffness.