title: Elevated pressure selectively blunts flow-evoked vasodilatation in rat mesenteric small arteries.
abstract: OBJECTIVE
  The present study investigated mechanisms underlying impaired endothelium-dependent vasodilatation elicited by elevating the intraluminal pressure in rat mesenteric small arteries.
  
  
  METHODS
  Arterial segments (internal diameter 316+/-2 microm, n=86) were mounted in a pressure myograph. The effect of elevating pressure from 50 to 120 mmHg for 1 h before resetting it to 50 mmHg was studied on endothelium-dependent vasodilatation.
  
  
  RESULTS
  In arteries constricted with U46619 in the presence of indomethacin, shear stress generated by flow, evoked vasodilatation that was abolished by an inhibitor of nitric oxide (NO) synthase, asymmetric dimethylarginine (1 mM), whereas acetylcholine-induced vasodilatation was unchanged. After elevation of intraluminal pressure for 1 h and then resetting it to 50 mmHg, vasodilatation induced by shear stress and the NO donor, S-nitrosopenicillamine was inhibited, while vasodilatation induced by a guanylyl cyclase activator, BAY 412272, and acetylcholine was unaltered. Superoxide levels sensitive to polyethylene glycol superoxide dismutase were increased in segments exposed to elevated pressure. A superoxide scavenger, tempol (300 microM), a general endothelin receptor antagonist, SB 217242 and the selective ET(A) receptor antagonist, BQ 123 preserved shear stress-evoked vasodilatation.
  
  
  CONCLUSIONS
  The present study shows that transient exposure to an elevated intraluminal pressure selectively inhibits flow-evoked NO-mediated vasodilatation, probably through activation of endothelin receptors and increased formation of superoxide. In contrast, elevation of pressure did not affect the acetylcholine-evoked endothelium-derived hyperpolarizing factor type vasodilatation in mesenteric small arteries.
authors.affiliation: Department of Pharmacology, University of Aarhus, 8000 Aarhus C, Denmark.
authors.forename: F H
authors.initials: FH
authors.lastname: Christensen
authors.forename: T
authors.initials: T
authors.lastname: Hansen
authors.forename: E
authors.initials: E
authors.lastname: Stankevicius
authors.forename: N H
authors.initials: NH
authors.lastname: Buus
authors.forename: U
authors.initials: U
authors.lastname: Simonsen
mesh_terms: D000109:Acetylcholine / Q000502:physiology; D000818:Animals; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013481:Superoxides / Q000378:metabolism; D014664:Vasodilation
chemical_list: C423582:3-(4-Amino-5-cyclopropylpyrimidine-2-yl)-1-(2-fluorobenzyl)-1H-pyrazolo(3,4-b)pyridine; D011720:Pyrazoles; D011725:Pyridines; C110881:S-nitro-N-acetylpenicillamine; D013481:Superoxides; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D010396:Penicillamine; D000109:Acetylcholine