title: Tranilast increases vasodilator response to acetylcholine in rat mesenteric resistance arteries through increased EDHF participation.
abstract: OBJECTIVE
  Tranilast, in addition to its capacity to inhibit mast cell degranulation, has other biological effects, including inhibition of reactive oxygen species, cytokines, leukotrienes and prostaglandin release. In the current study, we analyzed whether tranilast could alter endothelial function in rat mesenteric resistance arteries (MRA).
  
  
  METHODS
  Acetylcholine-induced relaxation was analyzed in MRA (untreated and 1-hour tranilast treatment) from 6 month-old Wistar rats. To assess the possible participation of endothelial nitric oxide or prostanoids, acetylcholine-induced relaxation was analyzed in the presence of L-NAME or indomethacin. The participation of endothelium-derived hyperpolarizing factor (EDHF) in acetylcholine-induced response was analyzed by preincubation with TRAM-34 plus apamin or by precontraction with a high K+ solution. Nitric oxide (NO) and superoxide anion levels were measured, as well as vasomotor responses to NO donor DEA-NO and to large conductance calcium-activated potassium channel opener NS1619.
  
  
  RESULTS
  Acetylcholine-induced relaxation was greater in tranilast-incubated MRA. Acetylcholine-induced vasodilation was decreased by L-NAME in a similar manner in both experimental groups. Indomethacin did not modify vasodilation. Preincubation with a high K+ solution or TRAM-34 plus apamin reduced the vasodilation to ACh more markedly in tranilast-incubated segments. NO and superoxide anion production, and vasodilator responses to DEA-NO or NS1619 remained unmodified in the presence of tranilast.
  
  
  CONCLUSIONS
  Tranilast increased the endothelium-dependent relaxation to acetylcholine in rat MRA. This effect is independent of the nitric oxide and cyclooxygenase pathways but involves EDHF, and is mediated by an increased role of small conductance calcium-activated K+ channels.
authors.affiliation: Departamento de Fisiologia e Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Pernambuco, Recife, Brazil.
authors.forename: Fabiano E
authors.initials: FE
authors.lastname: Xavier
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain; Instituto de Investigación Sanitaria IdIPaz, Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Blanco-Rivero
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain; Instituto de Investigación Sanitaria IdIPaz, Madrid, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Sastre
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain; Instituto de Investigación Sanitaria IdIPaz, Madrid, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Caracuel
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Callejo
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain; Instituto de Investigación Sanitaria IdIPaz, Madrid, Spain.
authors.forename: Gloria
authors.initials: G
authors.lastname: Balfagón
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D001685:Biological Factors / Q000502:physiology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology; D006834:Hydrazines / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000473:pathology; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000473:pathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013481:Superoxides / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology*; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
chemical_list: D001562:Benzimidazoles; D001685:Biological Factors; D006834:Hydrazines; D014665:Vasodilator Agents; C067410:endothelium-dependent hyperpolarization factor; D062367:ortho-Aminobenzoates; D013481:Superoxides; C086491:NS 1619; D009569:Nitric Oxide; C084012:1,1-diethyl-2-hydroxy-2-nitrosohydrazine; C012293:tranilast; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin