Abstract 316: Aortic Smooth Muscle Cell Stiffness as a Mechanism for the Increased Aortic Stiffness when Aging is Superimposed on Hypertension

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Abstract

It is generally recognized that increased aortic stiffness occurs in hypertension and aging. However, less is known about their combined influence on aortic stiffness. Furthermore, most prior studies have attributed increased aortic stiffness to changes in the extracellular matrix, whereas the hypothesis of this investigation is that a significant component of vascular stiffness resides at the level of the vascular smooth muscle cells (VSMCs), and that the contribution of this mechanism would be enhanced when aging is superimposed on hypertension. Accordingly, we examined aortic stiffness in young (16 wks) and old (64 wks) spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) wild type controls. We tested the hypothesis that the additional increase in aortic stiffness with combined aging and hypertension is mediated, in part, at the level of VSMCs. Systolic aortic pressure, measured by Millar micromanometer catheter, was significantly increased in the old compared to young SHR (191 ± 8 mmHg versus 148 ± 5 mmHg, p<0.01), but not in WKY (old, 101 ± 10 mmHg versus young, 120 ± 8 mmHg). Excised aortic ring segments were subjected to physiological levels of mechanical stretch ex vivo, and the wall stress in these ring segments was greater in older SHR than WKY (p<0.05). VSMCs were isolated from the thoracic aorta, and the stiffness of individual VSMCs was measured by atomic force microscopy nano-indentation. Isolated VSMC stiffness was 43 ± 8% greater, p<0.05, in old SHR compared to young SHR (27 ± 4 kPa). VSMC stiffness was also increased, p<0.05, in young SHR versus young WKY (14 ± 2 kPa), but this increase (92 ± 15%) was less, p<0.05, than that observed between old SHR versus old WKY (131 ± 2%). Thus, increased VSMC stiffness is a significant component of the increased aortic stiffness of hypertension, but this increase is augmented in aging hypertensive rats.

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