Vascular mechanical and contractile properties were compared in adult (6 months old) and very-aged (36 months old) Fischer 344/NNiaHSd X Brown Norway/BiNia (F344/NXBN) rats. Our previous work has indicated that aging is associated with aortic medial thickening. This morphological alteration was accompanied by a leftward shift in the aortic stress/strain curve indicating increased vessel stiffness in very-aged animals. Disruption of the endothelium as well as pretreatment of tissues with the nitric oxide (NO) donor sodium nitroprusside eliminated differences, suggesting a link between deficient endothelial NO release and reduced compliance in very-aged aortae. In addition, the Rho kinase inhibitor Y-27632 increased vessel compliance in both adult and very-aged tissues suggesting that the Rho cascade contributed to the stress/strain relationship. Maximal force developed in response to high potassium (K(+)) was reduced by approximately 70% in intact and endothelium-denuded aortae from very-aged rats. In contrast to contractile force development, calcium-dependent stress relaxation was increased in very-aged aorta. Finally, gel electrophoresis indicated a significantly higher tissue content of myosin heavy chain and a higher ratio of SM1/SM2 isoforms with aging. The results suggest multiple molecular changes with aging, which may be expected to alter vascular tissue function.