title: Opposite effect of mast cell stabilizers ketotifen and tranilast on the vasoconstrictor response to electrical field stimulation in rat mesenteric artery.
abstract: OBJECTIVE
  We analyzed whether mast cell stabilization by either ketotifen or tranilast could alter either sympathetic or nitrergic innervation function in rat mesenteric arteries.
  
  
  METHODS
  Electrical field stimulation (EFS)-induced contraction was analyzed in mesenteric segments from 6-month-old Wistar rats in three experimental groups: control, 3-hour ketotifen incubated (0.1 αmol/L), and 3-hour tranilast incubated (0.1 mmol/L). To assess the possible participation of nitrergic or sympathetic innervation, EFS contraction was analyzed in the presence of non-selective nitric oxide synthase (NOS) inhibitor L-NAME (0.1 mmol/L), α-adrenergic receptor antagonist phentolamine (0.1 µmol/L), or the neurotoxin 6-hydroxydopamine (6-OHDA, 1.46 mmol/L). Nitric oxide (NO) and superoxide anion (O2.(-) levels were measured, as were vasomotor responses to noradrenaline (NA) and to NO donor DEA-NO, in the presence and absence of 0.1 mmol/L tempol. Phosphorylated neuronal NOS (P-nNOS) expression was also analyzed.
  
  
  RESULTS
  EFS-induced contraction was increased by ketotifen and decreased by tranilast. L-NAME increased the vasoconstrictor response to EFS only in control segments. The vasodilator response to DEA-NO was higher in ketotifen- and tranilast-incubated segments, while tempol increased vasodilator response to DEA-NO only in control segments. Both NO and O2(-) release, and P-nNOS expression were diminished by ketotifen and by tranilast treatment. The decrease in EFS-induced contraction produced by phentolamine was lower in tranilast-incubated segments. NA vasomotor response was decreased only by tranilast. The remnant vasoconstriction observed in control and ketotifen-incubated segments was abolished by 6-OHDA.
  
  
  CONCLUSIONS
  While both ketotifen and tranilast diminish nitrergic innervation function, only tranilast diminishes sympathetic innnervation function, thus they alter the vasoconstrictor response to EFS in opposing manners.
authors: Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain.
authors: Esther
authors: E
authors: Sastre
authors: Laura
authors: L
authors: Caracuel
authors: Fabiano E
authors: FE
authors: Xavier
authors: Gloria
authors: G
authors: Balfagón
authors: Javier
authors: J
authors: Blanco-Rivero
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D004558:Electric Stimulation; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D006636:Histamine Release / Q000187:drug effects; D066298:In Vitro Techniques; D007665:Ketotifen / Q000494:pharmacology*; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology*; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D026602:Nitrergic Neurons / Q000187:drug effects / Q000502:physiology; D011189:Potassium Chloride / Q000494:pharmacology; D017208:Rats, Wistar; D013194:Staining and Labeling; D013481:Superoxides / Q000378:metabolism; D014048:Tolonium Chloride / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology; D014666:Vasomotor System / Q000187:drug effects; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
chemical_list: D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D062367:ortho-Aminobenzoates; D013481:Superoxides; D014048:Tolonium Chloride; D011189:Potassium Chloride; C012293:tranilast; D000109:Acetylcholine; D007665:Ketotifen
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