Abrupt increase in rat carotid blood flow induces rapid alteration of artery mechanical properties

Abstract

Vascular remodeling is essential to proper vessel function. Dramatic changes in mechanical environment, however, may initiate pathophysiological vascular remodeling processes that lead to vascular disease. Previous work by some of our group has demonstrated a dramatic rise in matrix metalloproteinase (MMP) expression shortly following an abrupt increase in carotid blood flow. We hypothesized that there would be a corresponding change in carotid mechanical properties. Unilateral carotid ligation surgery was performed to produce an abrupt, sustained increase in blood flow through the contralateral carotid artery of rats. The flow-augmented artery was harvested after sham surgery or 1, 2, or 6 days after flow augmentation. Vessel mechanical response in the circumferential direction was then evaluated through a series of pressure–diameter tests. Results show that the extent of circumferential stretch (normalized change in diameter) at in vivo pressure levels was significantly different ( p < 0.05 ) from normo-flow controls at 1 and 2 days following flow augmentation. Measurements at 1, 2, and 6 days were not significantly different from one another, but a trend in the data suggested that circumferential stretch was largest 1 day following surgery and subsequently decreased toward baseline values. Because previous work with this model indicated a similar temporal pattern for MMP-9 expression, an exploratory set of experiments was conducted where vessels were tested 1 day following surgery in animals treated with broad spectrum MMP inhibitors (either doxycycline or GM6001). Results showed a trend for the inhibitors to minimize changes in mechanical properties. Observations demonstrate that vessel mechanical properties change rapidly following flow augmentation and that alterations may be linked to expression of MMPs.