Vascular structural and mechanical alterations in hypertension and aging contribute towards cardiovascular morbidity/mortality^1-3. The aim of this study was to determine whether integrin-extracellular matrix (ECM) interactions contribute towards altered vascular structure and mechanics in hypertension and aging. The effect of disintegrin-treatment (kistrin, or echistatin) ex vivo on mesenteric artery structure and mechanics was assessed using wire-myography in spontaneously hypertensive rats (SHRs) and wistar-kyoto rats (WKYs). Integrin αV and α5 expression was also quantified using immunohistochemistry. Differences between data were tested using 2-tailed unpaired student’s t-test, or one-way ANOVA followed by Bonferroni’s correction for multiple comparisons. In arteries from 8 and 15 week-old SHRs versus WKYs, media/lumen ratios were greater (by 108 and 70% respectively; P<0.01) and media cross-sectional area (MCSA) and stiffness unaltered. Disintegrin-treatment of arteries did not alter structure or mechanics in SHRs versus control-treatment. With aging in WKYs, media thickness and MCSA were significantly increased (by 25 and 44% respectively in 15 week-old versus 8 week-old WKYs, P<0.05; by 43 and 46% respectively in >1 year-old versus 8 week-old WKYs, P<0.01) and stiffness unaltered. This was associated with unaltered integrin αV and α5 expression. In WKYs at all ages, disintegrin-treatment of arteries did not alter structure; however, stiffness was significantly reduced with echistatin-treatment versus control-treatment (P<0.05). These results suggest that integrin-ECM interactions are important determinants of passive stiffness in aging WKYs. Further insight into the role of integrin-ECM interactions on vascular structure and mechanics may have important implications for the reduction of cardiovascular morbidity/mortality.