title: Flow-induced relaxation of the rabbit middle cerebral artery is composed of both endothelium-dependent and -independent components.
abstract: OBJECTIVE
  The flow-induced relaxation of a branch of the rabbit middle cerebral artery was examined to determine if an endothelial-independent as well as -dependent component occurs in pial as well as systemic small arteries and the possible role of products of the cyclooxygenase and the L-arginine nitric oxide synthase pathways.
  
  
  METHODS
  Intraluminal flow was achieved by the infusion of a tissue bath solution into isometrically mounted rabbit pial arteries in a resistance artery myograph through a small pipette.
  
  
  RESULTS
  Intraluminal flow caused relaxation of the artery segment precontracted with 10 microM histamine. Treatment of endothelium-intact vessels with the nitric oxide synthase inhibitors NG-nitro-L-arginine (L-NNA) (100 microM) or NG-nitro-L-arginine methyl ester (L-NAME) (0.3 mM) significantly reduced the relaxation at flow rates of 5-30 microliters/min. This effect was partially reversed by 1 mM L-arginine. These inhibitors had no effect on the flow-induced relaxation of endothelium-denuded vessels. L-NNA did not influence the relaxation to 1 and 3 microM papaverine. Exposure to 10 microM aspirin, 10 microM indomethacin, or 300 nM tetrodotoxin had no effect on the flow-induced relaxation of either endothelium-intact or -denuded vessels (n = 6). Flow-induced relaxation was attenuated, but not abolished, by removal of the cerebrovascular endothelium. This reduction was not statistically significant.
  
  
  CONCLUSIONS
  These results show that intraluminal flow caused relaxation of a branch of the rabbit middle cerebral artery, in part through a mechanism sensitive to inhibitors of nitric oxide synthase, most likely the generation of nitric oxide from the vascular endothelium. The major component of the relaxant response is independent of the endothelium and of nitric oxide synthesis through an L-NNA- or L-NAME-sensitive mechanism. The relaxation does not involve cyclooxygenase products nor neurogenic mediators. These results suggest that pial arteries, like those of the rabbit ear, exhibit a novel mechanism for the flow-induced relaxation of agonist-induced tone that is intrinsic to the tissues of the vascular wall subjacent to the endothelium.
authors.affiliation: Department of Pharmacology, University of Vermont, College of Medicine, Burlington 05405-0068.
authors.forename: A J
authors.initials: AJ
authors.lastname: Gaw
authors.forename: J A
authors.initials: JA
authors.lastname: Bevan
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001783:Blood Flow Velocity; D002536:Cerebral Arteries / Q000187:drug effects / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology*; D006632:Histamine; D019331:NG-Nitroarginine Methyl Ester; D019335:Nitroarginine; D011817:Rabbits; D014664:Vasodilation / Q000502:physiology*
chemical_list: D019335:Nitroarginine; D006632:Histamine; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester