Differential Effects of Reduced Cyclic Stretch and Perturbed Shear Stress Within the Arterial Wall and on Smooth Muscle Function

BACKGROUND: Cyclic circumferential stretch and shear stress act in concert and yet are capable of independently mediating arterial smooth muscle function, modulating the production of superoxide and stimulating arterial remodeling. METHODS: Porcine carotid arteries were perfused ex vivo for 72 h. Groups combining normal (5%) and reduced (1%) stretch with high shear (6 +/- 3 dyn/cm2) and oscillatory shear (0.3 +/- 3 dyn/cm2) stress were created, while maintaining a pulse pressure of 80 +/- 10 mm Hg. RESULTS: Total superoxide production, fibronectin expression, and gelatinase activation were mediated by shear stress, but expression in the endothelial region was mediated by reduced cyclic stretch. By plotting intensity vs. radius, we saw that superoxide and gelatinase activity were in part mediated by stress distributions throughout the vascular wall, whereas fibronectin and p22-phox were much less or not at all. These findings, when coupled with our results from tissue reactive studies, suggest that the arterial remodeling process triggered in the endothelial region due to reduced stretch causes the most significant changes in arterial smooth muscle function. CONCLUSIONS: We have found that the remodeling process triggered by reduced compliance in the endothelial region of large conduit arteries has a more profound detrimental effect to smooth muscle function than that brought on by perturbed shear stress. This work provides new insight by suggesting that although mechanical stimuli such as cyclic stretch and shear stress are known to augment similar markers of vascular remodeling, the location of their expression throughout the vascular wall differs greatly and this can have dramatic effects on vascular function.