Role of endothelium in shear stress-induced constrictions in rat middle cerebral artery

• Published in: Stroke (1970) Vol. 32; no. 6; pp. 1394 - 1400
• Main Authors: BRYAN, Robert M, STEENBERG, Marie L, MARRELLI, Sean P
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01-06-2001; American Heart Association, Inc
• Subjects: 1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt - pharmacology; Animals; Antioxidants - pharmacology; Biological and medical sciences; Blood Flow Velocity - physiology; Calcium - metabolism; Catalase - pharmacology; Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges; Charybdotoxin - pharmacology; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; Enzyme Inhibitors - pharmacology; Fluorescent Dyes; Free Radical Scavengers - pharmacology; Fundamental and applied biological sciences. Psychology; Fura-2; In Vitro Techniques; Male; Middle Cerebral Artery - cytology; Middle Cerebral Artery - drug effects; Middle Cerebral Artery - physiology; NG-Nitroarginine Methyl Ester - pharmacology; Rats; Rats, Long-Evans; Reactive Oxygen Species - metabolism; Stress, Mechanical; Superoxide Dismutase - pharmacology; Vasoconstriction - drug effects; Vasoconstriction - physiology; Vertebrates: nervous system and sense organs; Rat; Rodentia; Central nervous system; Middle cerebral artery; Vasoconstriction; Exploration; Free radical; Endothelium; Vertebrata; Mammalia; Calcium ion; Blood vessel; Animal; Shear stress; Circulatory system; Hemodynamics; Brain (vertebrata)
• ISSN: 0039-2499; 1524-4628
• DOI: 10.1161/01.STR.32.6.1394

Luminal shear stress has been reported to constrict cerebral arteries and arterioles of several species. Although the endothelium is not required for this response, it is not known whether the endothelium enhances or attenuates shear stress-induced constrictions.
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 Ca(2+) concentration. Luminal shear stress was increased by adjusting luminal flow while maintaining a constant intraluminal pressure.
After the development of spontaneous tone in MCAs without luminal flow, inside diameters were approximately 190 microm. MCAs constricted approximately 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 with 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 had been removed. In intact vessels, endothelial Ca(2+) increased 33 nmol/L (from 133+/-11 to 166+/-12 nmol/L) when shear stress was increased to 50 dyne/cm(2). The presence of N(G)-nitro-L-arginine methyl ester (L-NAME), L-NAME+indomethacin, or L-NAME+indomethacin+charybdotoxin had no significant effect on the shear stress-induced constrictions in MCAs with intact endothelium.
We conclude that the endothelium plays a role in attenuating the shear stress-induced constrictions in rat MCAS: The attenuation does not appear to be by release of NO, prostacyclin, or endothelium-derived hyperpolarizing 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 abluminal side of the vessel.