Shear level influences resistance artery remodeling: wall dimensions, celldensity, and eNOS expression

The magnitude of shear stimulus has been shown to determine the level of gr owth factor expression in cell culture. However, little is known regarding what effect shear level has on specific arterial wall remodeling events in vivo. We have hypothesized that the rate of luminal diameter change and spe cific remodeling events within the arterial wall layers are dependent on sh ear level. Selective ligations were made to alter the number of microvascul ar perfusion units of mesenteric arteries within the same animal to similar to 50%, 200%, and 400% of control. Arterial blood flow and wall shear rate were correlated with the degree of alteration in perfusion units. Luminal diameters were decreased in 50% arteries by day 2 and increased similar to 17% and 33%, respectively, in 200% and 400% arteries at day 7. The rate of diameter change was greatest in 50% and 400% arteries. Wall areas (medial 37%; intimal +18% at day 2) and cell densities (intimal +26%; adventitial 44% at day 2) were altered only in the 400% arteries. A positive correlatio n existed by day 2 between endothelial staining for endothelial nitric oxid e synthase and shear level. The results demonstrate that shear level influe nces the rate of luminal expansion, specific remodeling events within each wall layer, and the degree of endothelial gene expression. A greater unders tanding of how shear level influences specific remodeling events within eac h wall layer should aid in the development of targeted therapies to manipul ate the remodeling process in health and disease.