Effects of luminal shear stress on cerebral arteries and arterioles

Abstract

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 β3-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/cm2constricted 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 β3-chain are involved with the shear stress-induced constrictions.