title: Integrin signaling, free radicals, and tyrosine kinase mediate flow constriction in isolated cerebral arteries.
abstract: Isolated, cannulated, and pressurized (100 mmHg) middle cerebral arteries from adult cats were perfused intraluminally at rates from 0 to 4 ml/min with heated and gassed physiological saline solution. An electronic system held pressure constant by changing outflow resistance. The arteries constricted 18.1 +/- 0.95% in response to flow and depolarized from -54 +/- 0.51 to -40 +/- 1.26 mV (P < 0.05). Constriction was independent of a functional endothelium but was eliminated by superoxide dismutase or tyrosine kinase inhibitors. Luminal perfusion with a synthetic extracellular matrix Arg-Gly-ASP (RGD) peptide that binds with integrin significantly reduced constriction to flow. Neither reducing intraluminal pressure nor increasing tone or shear stresses altered constriction to flow. Flow-induced constriction did not impede the ability of the arteries to dilate to hypercapnia, and inhibiting flow-induced constriction did not alter contractile responses to other agonists. These data suggest that, in vitro, middle cerebral arteries constrict to flow through a mechanism involving free radicals and tyrosine kinase and that flow shear stresses resulting in constriction are transduced by integrin signaling.
authors.affiliation: Department of Neurology, The Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA. jmadden@mcw.edu
authors.forename: J A
authors.initials: JA
authors.lastname: Madden
authors.forename: N J
authors.initials: NJ
authors.lastname: Christman
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity; D001794:Blood Pressure; D002415:Cats; D005260:Female; D066298:In Vitro Techniques; D016023:Integrins / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D020768:Middle Cerebral Artery / Q000187:drug effects / Q000502:physiology*; D009119:Muscle Contraction / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D013314:Stress, Mechanical; D013482:Superoxide Dismutase / Q000494:pharmacology; D014655:Vascular Resistance; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
chemical_list: D016023:Integrins; D013482:Superoxide Dismutase; D011505:Protein-Tyrosine Kinases; D019331:NG-Nitroarginine Methyl Ester