Shear stress is differentially regulated among inbred rat strains.
An important compensatory response to atherosclerosis is vascular remodeling, with maintenance of vessel lumen diameter and shear stress. Both hemodynamic and environmental factors contribute to vascular remodeling and shear stress regulation, and the process is probably also influenced by genetic factors. To establish an animal model for genetic analysis of shear stress regulation and vascular remodeling, we studied the effects of chronic flow alteration in four inbred rat strains. By ligating the left internal and external carotid arteries, we caused a approximately 90% decrease in left common carotid blood flow and a approximately 50% increase in right (contralateral) common carotid flow. After 4 weeks of altered flow, there were significant interstrain differences with respect to the change in carotid outer diameter (OD), the relationship between flow and shear stress, and the extent to which shear stress was normalized. Genetically hypertensive rats (GH) exhibited the greatest reduction in shear stress in response to increased flow, stroke-prone spontaneously hypertensive rats (SHR-SP) exhibited a smaller response, and Brown Norway (BN) rats exhibited the smallest response. SHR-SP and GH also differed significantly in outward remodeling (defined as an increase in lumen and vessel diameter) in increased flow arteries. In response to decreased flow, BN rats exhibited the smallest reduction in shear stress. These findings demonstrate significant strain-dependent differences in shear stress regulation and vascular remodeling in response to altered flow. This study emphasizes the important role of genetic factors in vascular remodeling and suggests that genetic analysis of these strains will provide novel insights into the underlying mechanisms.
Ibrahim
Jamila
J
Center for Cardiovascular Research, Department of Medicine, University of Rochester, 601 Elmwood Ave, Rochester, NY 14642, USA.
Miyashiro
Jody K
JK
Berk
Bradford C
BC
D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology; D002339:Carotid Arteries / Q000033:anatomy & histology / Q000201:enzymology / Q000502:physiology*; D002455:Cell Division; D007150:Immunohistochemistry; D008026:Ligation; D008297:Male; D023421:Models, Animal; D019001:Nitric Oxide Synthase / Q000276:immunology / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D051381:Rats; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow; D013045:Species Specificity; D013314:Stress, Mechanical
D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat