Abstract 15: Increased Intrinsic Stiffness of Aortic Vascular Smooth Muscle Cells as a Mechanism for Increased Aortic Stiffness in Spontaneously Hypertensive Rats
An increase in vascular stiffness is a fundamental component of hypertension. Our hypothesis is that increased large artery stiffness in hypertension is due in part to intrinsic mechanical properties of vascular smooth muscle cells (VSMC). Adult spontaneously hypertensive rats (SHR) (16 weeks old) and age-matched Wistar-Kyoto normotensive (WKY) rats were studied. Aortic pressure, measured with a Millar catheter, was higher in SHR than WKY (MAP 123±4 versus 96±6 mmHg, p<0.05). Aortic stiffness, measured with pulse wave velocity, in vivo, was 2 to 2.5 fold higher in SHR rats (7.65 mm/ms) compared to normotensive rats(3.27 mm/ms, p<0.01). Aortic VSMCs were isolated from the SHR and WKY rats. Stiffness in single VSMC was continuously recorded in vitro using atomic force microscopy and temporal oscillations in VSMC elasticity, which represent the dynamic properties of elasticity, were observed and analyzed by Eigen decomposition. VSMC stiffness was consistently increased by 1.5 to 2 fold in SHR (24.0 kPa) versus WKY (11.8 kPa) (p<0.05). Moreover, the oscillations in elasticity were significantly different between the two groups in terms of frequency and amplitude (p<0.05). ML-7, a highly specific inhibitor of myosin light chain kinase (MLCK), produced a greater reduction in the VSMC elasticity from SHR aorta compared to WKY rats (p<0.05), and also eliminated the difference between the SHR and WKY. Furthermore, ML-7 altered the oscillation in VSMC elasticity in SHR, but not WKY. These observations indicate that there is an inherently altered VSMC stiffness in hypertension that is associated with unique dynamic cytoskeletal behavior. These dynamic elements may be involved mechanistically in increasing aortic stiffness in SHR rats. MLCK participates in the regulation of VSMC stiffness in hypertension via altering both basal VSMC elasticity and temporal oscillations.
- © 2012 by American Heart Association, Inc.