Effects of luminal shear stress on cerebral arteries and arterioles

The effect of luminal shear stress was studied in cerebral arteries and art erioles. Middle cerebral arteries (MCA) and penetrating arterioles (PA) wer e isolated from male Long-Evans rats, mounted in a tissue bath, and pressur ized. After the development of spontaneous tone, inside diameters were 186 +/- 5 mum (n = 28) for MCA and 65 +/- 3 mum (n = 37) for PA. MCA and PA con stricted similar to 20% with increasing flow. Flow-induced constriction per sisted in MCA and PA after removal of the endothelium. After removal of the endothelium, the luminal application of a polypeptide containing the Arg-G ly-Asp amino acid sequence (inhibitor of integrin attachment) abolished the flow-induced constriction. Similarly, an antibody specific for the beta (3 )-chain of the integrin complex significantly inhibited the flow-induced co nstriction. The shear stress-induced constriction was accompanied by an inc rease in vascular smooth muscle Ca2+. For example, a shear stress of 20 dyn /cm(2) constricted MCA 8% (n = 5) and increased Ca2+ from 209 +/- 17 to 262 +/- 29 nM (n = 5). We conclude that isolated cerebral arteries and arterio les from the rat constrict to increased shear stress. Because the endotheli um is not necessary for the response, the shear forces must be transmitted across the endothelium, presumably by the cytoskeletal matrix, to elicit co nstriction. Integrins containing the beta (3)-chain are involved with the s hear stress-induced constrictions.