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Departments of 1 Anesthesiology, 2 Molecular Physiology and Biophysics, and 3 Division of Cardiovascular Sciences, Department of Medicine, Baylor College of Medicine, Houston, Texas 77030
The effect of luminal shear stress was
studied in cerebral arteries and arterioles. Middle cerebral arteries
(MCA) and penetrating arterioles (PA) were isolated from male
Long-Evans rats, mounted in a tissue bath, and pressurized. After the
development of spontaneous tone, inside diameters were 186 ± 5 µm (n = 28) for MCA and 65 ± 3 µm
(n = 37) for PA. MCA and PA constricted ~20% with
increasing flow. Flow-induced constriction persisted in MCA and PA
after removal of the endothelium. After removal of the endothelium, the
luminal application of a polypeptide containing the Arg-Gly-Asp amino
acid sequence (inhibitor of integrin attachment) abolished the
flow-induced constriction. Similarly, an antibody specific for the
3-chain of the integrin complex significantly inhibited the flow-induced constriction. The shear stress-induced constriction was accompanied by an increase in vascular smooth muscle
Ca2+. For example, a shear stress of 20 dyn/cm2
constricted MCA 8% (n = 5) and increased
Ca2+ from 209 ± 17 to 262 ± 29 nM
(n = 5). We conclude that isolated cerebral arteries
and arterioles from the rat constrict to increased shear stress.
Because the endothelium is not necessary for the response, the shear
forces must be transmitted across the endothelium, presumably by the
cytoskeletal matrix, to elicit constriction. Integrins containing the
3-chain are involved with the shear stress-induced constrictions.
cerebrovascular circulation; endothelium; integrins; cremaster muscle arteriole; calcium; fura 2
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