Opposite effect of mast cell stabilizers ketotifen and tranilast on the vasoconstrictor response to electrical field stimulation in rat mesenteric artery
Entity
UAM. Departamento de FisiologíaPublisher
Public Library of ScienceDate
2013-01-01Citation
10.1371/journal.pone.0073232
Plos One 8.8 (2013): e73232
ISSN
1932-6203 (online)DOI
10.1371/journal.pone.0073232Funded by
This work was supported by grants from Ministerio de Ciencia e Innovación (SAF2009-10374), Ministerio de Economía y Competitividad (SAF2012-38530) and Fundación MapfreSubjects
Acetylcholine; Electric Stimulation; In Vitro Techniques; Mast Cells; Mesenteric Arteries; Vasoconstriction; MedicinaRights
© 2013 Sastre et al.Abstract
Objectives: 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-monthold
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.
Conclusion: 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
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Google Scholar:Sastre, Esther
-
Caracuel, Laura
-
Xavier, Fabiano Elias
-
Balfagón Calvo, Gloria
-
Blanco Rivero, Javier
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