Opposite Effect of Mast Cell Stabilizers Ketotifen and Tranilast on the Vasoconstrictor Response to Electrical Field Stimulation in Rat Mesenteric ArteryReport as inadecuate




Opposite Effect of Mast Cell Stabilizers Ketotifen and Tranilast on the Vasoconstrictor Response to Electrical Field Stimulation in Rat Mesenteric Artery - Download this document for free, or read online. Document in PDF available to download.

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-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.

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.



Author: Esther Sastre , Laura Caracuel , Fabiano E. Xavier, Gloria Balfagón, Javier Blanco-Rivero

Source: http://plos.srce.hr/



DOWNLOAD PDF




Related documents