Abstract 230: Regional Variation in Intrinsic Mechanics of Arterial Vascular Smooth Muscle Cells in Spontaneously Hypertensive Rats

Abstract

Aims: An increased aortic stiffness is a fundamental manifestation of hypertension (HT). Our previous study showed that intrinsic mechanical properties of aortic vascular smooth muscle cells (VSMC) are an important contributor to the increased large artery stiffness in HT. However, whether VSMC mechanics of smaller arteries is also altered in HT remains unknown. The goal of this study is to test our hypothesis that the VSMC elastic and adhesive properties vary along the arterial tree reflecting the regional heterogeneities of physiological loading and geometric properties of the artery wall. Methods and Results: Primary VSMCs were isolated from the thoracic aorta (TA) and renal artery (RA) of adult spontaneously hypertensive rats (SHR) (16 weeks old, male) and age-matched Wistar-Kyoto normotensive (WKY) rats. Atomic force microscopy (AFM) was used to measure mechanical properties of individual VSMC at 37°C. Local apparent elastic modulus (Eap) was determined using Hertz contact analysis for a cone to model the indentation force curve, and maximum adhesion force (Fad) was obtained from the retraction force curve; results were shown as mean (±SD) (n=10 cells per condition) and compared using two way ANOVA. Eap of VSMCs from the TA was significantly higher in SHR (7.0± 1.3 kPa) vs. WKY (5.3 ± 1.5 kPa; p < 0.001) and Fad was significantly larger in SHR (39.9 7.2 pN) vs. WKY (30.6 10.9 pN; p < 0.01). No difference was found between SHR and WKY in VSMCs from renal artery in terms of Eap (4.5 0.8 kPa vs. 4.8 0.9 kPa; p = 0.59) and Fad (23.1 5.2 pN vs. 28.0 7.0 pN; p = 0.17). Although no difference was observed in cell shape represented by the cellular length:width ratio (p > 0.25), stiffness and adhesion of VSMC from TA were significantly higher vs. RA in SHR (p<0.0001) but not in WKY (P>0.35), indicating that the altered mechanics of VSMC in hypertension is more prominent in the large conduction vessel compared to the small artery. Conclusion: Intrinsic stiffness and adhesion of isolated VSMC are elevated preferentially in the thoracic aorta of SHR rats; the regional variations may associate mechanistically with increased aortic tissue stiffness in hypertension.