© 1997 American Heart Association, Inc.
Articles |
Flow-Induced Vascular Remodeling in the Rat Carotid Artery Diminishes With Age
From the Department of Medicine, Division of Cardiology, University of Washington, Seattle.
Correspondence to Dr Bradford C. Berk, Division of Cardiology, Box 357710, University of Washington, Seattle, WA 98195. E-mail bcberk{at}u.washington.edu
Abstract Vascular remodeling is regulated by a combination of
hemodynamic, environmental, and genetic factors and may
be influenced by age. To evaluate age-dependent remodeling in rats, we
developed and used a quantitative highly reproducible model of carotid
flow alteration. Fourteen juvenile (99±3 g) and 9 adult (199±5 g)
male inbred Fischer rats underwent ligation of the left internal and
external carotid arteries under anesthesia. Left common
carotid blood flow immediately decreased by 
93%, whereas flow in
the contralateral carotid increased by 46%. After 4 weeks, the left
carotid outer diameter (OD) significantly decreased in both juvenile
and adult rats (as measured in vivo and by histological
morphometry) compared with sham-operated rats. Changes in shear stress
acutely mirrored the changes in blood flow. OD increased and shear
stress returned to initial values after chronic exposure to increased
flow in juvenile but not adult rats. To develop a simple quantitative
index of remodeling that would not require killing the animals, we
measured the OD in vivo and compared the ratio of right to left OD (OD
ratio [ODR]) between groups. The initial ODR for all groups was
1.0. After 4 weeks of altered flow, the ODR was significantly
greater in juvenile than in adult rats (1.48±0.05 versus 1.29±0.04,
respectively; P=.030), indicating that juvenile rats
experienced more extensive remodeling than did the adult rats. We also
found that unilateral carotid ligation caused a left versus right
difference in endothelial NO synthase protein levels
after 4 weeks that was not present in the sham-operated animals.
Thus, the model described here shows that flow-induced vascular
remodeling is dependent on age and supports the hypothesis that the
driving force for remodeling involves shear stress and possibly NO.
Because the model is quantitative, it allows dissection of the genetic
factors that regulate remodeling in inbred rat strains.
Key Words: outer diameter ratio • shear stress • endothelial nitric oxide synthase
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