Background and Purpose-Luminal shear stress has been reported to constrict
cerebral arteries and arterioles of several species. Although the endotheli
um is not required for this response, it is not known whether the endotheli
um enhances or attenuates shear stress-induced constrictions.
Methods-Middle cerebral arteries (MCAs) were isolated from male Long-Evans
rats, mounted in a tissue bath, and pressurized to 80 mm Hg in the absence
of luminal flow. In some MCAs, the endothelium was selectively loaded with
fura 2 for the measurement of endothelial Ca2+ concentration. Luminal shear
stress was increased by adjusting luminal flow while maintaining a constan
t intraluminal pressure.
Results-After the development of spontaneous tone in MCAs without luminal f
low, inside diameters were approximate to 190 mum. MCAs constricted approxi
mate to 15% when luminal flow was increased to produce a shear stress of 50
dyne/cm(2). The shear stress-induced constrictions were more pronounced in
vessels without intact endothelium, Scavenging reactive oxygen species wit
h 4,5-dihydroxy-1,3-benzene disulfonic acid (Tiron) or superoxide dismutase
/catalase significantly inhibited the shear stress-induced constrictions in
vessels with intact endothelium and in vessels in which the endothelium ha
d been removed. In intact vessels, endothelial Ca2+ increased 33 nmol/L (fr
om 133 +/- 11 to 166 +/- 12 nmol/L) when shear stress was increased to 50 d
yne/cm2. The presence of NG-nitro-L-arginine methyl ester (L-NAME), L-NAMEindomethacin, or L-NAME+indomethacin+charybdotoxin had no significant effec
t on the sheer stress-induced constrictions in MCAs with intact endothelium
.
Conclusions-We conclude that the endothelium plays a role in attenuating th
e shear stress-induced constrictions in rat MCAs. The attenuation does not
appear to be by release of NO, prostacyclin, or endothelium-derived hyperpo
larizing factor. The endothelium apparently attenuates the constriction by
an unknown dilating factor, by a dilating process, or simply by attenuating
the mechanical force of the shear stress as it is transmitted to the ablum
inal side of the vessel.